Background The present study was undertaken to replicate the associations of representative polymorphisms in three genes （complement factor H （CFH）, complement factor B （BF） and HtrA serine peptidase 1 （HTRA1）...Background The present study was undertaken to replicate the associations of representative polymorphisms in three genes （complement factor H （CFH）, complement factor B （BF） and HtrA serine peptidase 1 （HTRA1）） with exudative age-related macular degeneration （AMD） in a Han Chinese population, and to test if the modifiable environmental factors affect AMD susceptibility associated with different type of genotype in these genes. Methods An age, gender and ethnicity matched case-control study was conducted to genotype the representative single neucleotide polymorphisms （SNPs） loci including rs1061170 and rs1410996 in CFH, rs641153 and rs4151667 in BF and rs11200638 in HTRA1 gene in 144 exudative AMD patients and 126 normal controls using PCR-RFLP and direct resequencing. The demographic characteristics and behavioral risk factors were also recorded. Allelic and genotypic associations for individual SNP and joint associations with two loci were performed. The gene-gene and gene-environment interactions were analyzed using multivariate non-conditional Logistic regression analysis. Results The C risk allele frequencies for CFH Y402H （rs1061170） in cases and controls were 12.5% and 5.4% respectively, which were much lower than those in Caucasians （P 〈0.001）. Compared with TT homozygous genotype, the CT heterozygous genotype was positively associated with AMD with odds ratio （OR） of 3.23 （1.36-5.07）. However, the population attributable risk （PAR） of C allele was only 3.3% （1.4%-4.3%）. rs1410996 was also associated with AMD independent of Y402H. The ORs of exudative AMD for individuals carrying one copy risk allele and two copy risk alleles were 2.57 （1.21-5.45） and 4.76 （2.15-10.55） respectively, with correspondent PARs of 28.3% （2.0%-40.5%） and 38.2% （21.8%-45.4%）. rs11200636 in HTRA1 was another susceptible locus for AMD and the risk homozygotes were significantly susceptible for exudutive AMD （OR=3.98, 1.88-8.43） with PAR of 38.9% （24.3%-45.8%）展开更多
Objective To evaluate the effects of environmental factors and microRNAs （miRNAs） （miR-126, miR-143, and miR-145） on the risk of coronary heart disease （CHD）. Methods A frequency-matched case-control study （450...Objective To evaluate the effects of environmental factors and microRNAs （miRNAs） （miR-126, miR-143, and miR-145） on the risk of coronary heart disease （CHD）. Methods A frequency-matched case-control study （450 patients, 450 controls） was conducted from April 2014 to December 2016 in Fuzhou City, China. Environmental factors were investigated using a self-administered questionnaire, and the expression levels of miR-126, rniR-143, and miR-145 were determined by quantitative real-time Polymerase Chain Reaction （PCR） in pe- ripheral blood mononuclear cells. Unconditional logistic regression models were used for statistical evaluation. Results Alcohol consumption, high-salt diets, high-intensity work, and lack of physical activity were significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. MiR-126, miR-143, and miR-145 were highly expressed in the CHD group compared with the control group. After adjustment for other environmental factors, unconditional logistic regression results revealed that miR-126, miR-143, and depression were the independent risk factors of CHD, and light diet was the independent protective factor of CHD. Conclusions Our data suggest that a family history of CHD, anxiety, and alcohol consumption was significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. Furthermore, miR-126 and miR-143 in combination with several risk factors, could play a joint role in the development of CHD. Therefore, it is necessary to manage patients with CHD in all directions and multiple level.展开更多
Inflammation plays a significant role in the etiology of type 2 diabetes mellitus(T2DM).The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury,o...Inflammation plays a significant role in the etiology of type 2 diabetes mellitus(T2DM).The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury,oxidative stress and beta cell apoptosis in T2 DM.Among the recognized markers are interleukin(IL)-6,IL-1,IL-10,IL-18,tissue necrosis factor-alpha(TNF-α),C-reactive protein,resistin,adiponectin,tissue plasminogen activator,fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance.Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatory cytokines have been reported as a risk for T2 DM.Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups.The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions.This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6,TNF-α,resistin and adiponectin in pathogenesis of T2 DM.展开更多
AIM: To examine the effect of the potential interaction between KIF1 B variants(rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma(HCC) in a high-risk region in China.METHODS: ...AIM: To examine the effect of the potential interaction between KIF1 B variants(rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma(HCC) in a high-risk region in China.METHODS: Three hundred and six patients with HCC and 306 hospital-based control participants residing in the Shunde region of Guangdong Province, China were enrolled. Clinical characteristics were collected by reviewing the complete medical histories from the patient archives, and epidemiological data were collected using a questionnaire and clinical examination. Two single nucleotide polymorphisms(SNPs) of KIF1B(rs17401966 and rs3748578) were chosen for the current study. All subjects were genotypedusing a Taq Man real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions.RESULTS: Smoking, frequent consumption of raw freshwater fish, hepatitis B virus(HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio(OR) = 12.02; 95% confidence interval(95%CI): 6.02-24.00]. No significant association was found between the KIF1 B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption(P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC(OR = 2.36; 95%CI: 1.49-3.74).CONCLUSION: The gene-environment interaction between the KIF1 B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.展开更多
BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings.Recent advancements in genetic and epigenetic research have provided ...BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings.Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD,influencing both diagnosis and therapeutic strategies.AIM To explore the genetic architecture of ASD,elucidate mechanistic insights into genetic mutations,and examine gene-environment interactions.METHODS A comprehensive systematic review was conducted,integrating findings from studies on genetic variations,epigenetic mechanisms(such as DNA methylation and histone modifications),and emerging technologies[including Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)-Cas9 and single-cell RNA sequencing].Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar.RESULTS Genetic studies have identified numerous risk genes and mutations associated with ASD,yet many cases remain unexplained by known factors,suggesting undiscovered genetic components.Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving.Epigenetic modifications,particularly DNA methylation and non-coding RNAs,also play significant roles in ASD pathogenesis.Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data.CONCLUSION Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments.Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice.Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies,ultimately enhancing outcomes for展开更多
Evidence from epidemiological studies suggest a relationship between cigarette smoking and low risk of Parkinson disease(PD).As a major component of tobacco smoke,nicotine has been proposed to be a substance for preve...Evidence from epidemiological studies suggest a relationship between cigarette smoking and low risk of Parkinson disease(PD).As a major component of tobacco smoke,nicotine has been proposed to be a substance for preventing against PD risk,with a key role in regulating striatal activity and behaviors mediated through the dopaminergic system.Animal studies also showed that nicotine could modulate dopamine transmission and reduce levodopa-induced dyskinesias.However,previous clinical trials yield controversial results regarding nicotine treatment.In this review,we updated epidemiological,preclinical and clinical data,and studies on nicotine from diet.We also reviewed interactions between genetic factors and cigarette smoking.As a small amount of nicotine can saturate a substantial portion of nicotine receptors in the brain,nicotine from other sources,such as diet,could be a promising therapeutic substance for protection against PD.展开更多
Background:Severe liver disease(SLD),including cirrhosis and liver cancer,constitutes a major disease burden in China.We aimed to examine the association of genetic and healthy lifestyle factors with the incidence and...Background:Severe liver disease(SLD),including cirrhosis and liver cancer,constitutes a major disease burden in China.We aimed to examine the association of genetic and healthy lifestyle factors with the incidence and prognosis of SLD.Methods:The study population included 504,009 participants from the prospective China Kadoorie Biobank aged 30-79 years.The individuals were from 10 diverse areas in China without a history of cancer or liver disease at baseline.Cox regression was used to estimate adjusted hazard ratios(HRs)for incident SLD and death after SLD diagnosis associated with healthy lifestyle factors(smoking,alcohol,physical activity,and central adiposity).Additionally,the contribution of genetic risk for hepatitis B virus(HBV,assessed by genetic variants in major histocompatibility complex,class II,DP/DQ[HLA-DP/DQ]genes)was also estimated.Results:Compared with those with 0-1 healthy lifestyle factor,participants with 2,3,and 4 factors had 12%(HR 0.88[95%confidence interval[CI]0.85,0.92]),26%(HR 0.74[95%CI:0.69,0.79]),and 44%(HR 0.56[95%CI:0.48,0.65])lower risks of SLD,respectively.Inverse associations were observed among participants with both low and high genetic risks(HR per 1-point increase 0.83[95%CI:0.74,0.94]and 0.91[95%CI:0.82,1.02],respectively;P_(interaction)=0.51),although with a non-significant trend among those with a high genetic risk.Inverse associations were also observed between healthy lifestyle factors and liver biomarkers regardless of the genetic risk.Despite the limited power,healthy lifestyle factors were associated with a lower risk of death after incident SLD among participants with a low genetic risk(HR 0.59[95%CI:0.37,0.96]).Conclusions:Lifestyle modification may be beneficial in terms of lowering the risk of SLD regardless of the genetic risk.Moreover,it is also important for improving the prognosis of SLD in individuals with a low genetic risk.Future studies are warranted to examine the impact of healthy lifestyles on SLD prognosis,particularly among individuals with a high ge展开更多
Identifying mechanisms and pathways involved in gene–environment interplay and phenotypic plasticity is a long-standing challenge.It is highly desirable to establish an integrated framework with an environmental dime...Identifying mechanisms and pathways involved in gene–environment interplay and phenotypic plasticity is a long-standing challenge.It is highly desirable to establish an integrated framework with an environmental dimension for complex trait dissection and prediction.A critical step is to identify an environmental index that is both biologically relevant and estimable for new environments.With extensive field-observed complex traits,environmental profiles,and genome-wide single nucleotide polymorphisms for three major crops(maize,wheat,and oat),we demonstrated that identifying such an environmental index(i.e.,a combination of environmental parameter and growth window)enables genome-wide association studies and genomic selection of complex traits to be conducted with an explicit environmental dimension.Interestingly,genes identified for two reaction-norm parameters(i.e.,intercept and slope)derived from flowering time values along the environmental index were less colocalized for a diverse maize panel than for wheat and oat breeding panels,agreeing with the different diversity levels and genetic constitutions of the panels.In addition,we showcased the usefulness of this framework for systematically forecasting the performance of diverse germplasm panels in new environments.This general framework and the companion CERIS-JGRA analytical package should facilitate biologically informed dissection of complex traits,enhanced performance prediction in breeding for future climates,and coordinated efforts to enrich our understanding of mechanisms underlying phenotypic variation.展开更多
There have been few studies on the association between vitamin D levels and gastric cancer in Asian populations,but no studies have been performed on the interactions between vitamin D intake and polymorphisms in the ...There have been few studies on the association between vitamin D levels and gastric cancer in Asian populations,but no studies have been performed on the interactions between vitamin D intake and polymorphisms in the vitamin D pathway.The effects of vitamin D intake,vitamin D related genetic polymorphisms,and their association with the incidence of gastric cancer were investigated in a hospital case-control study,including 715 pairs of newly diagnosed gastric cancer patients and controls matched for age and sex.Correlations between vitamin D intake and plasma vitamin D concentrations were also assessed in a subset of subjects.No statistically significant difference was observed in the dietary intake of vitamin D between the patients and controls,nor were there any evident associations between vitamin D intake and risk of gastric cancer in multivariate analyses.Vitamin D intake significantly correlated with the circulating 25-hydroxyvitamin D levels,but not with the active form of the vitamin,1,25-dihydroxyvitamin D.There were no statistically significant interactions between vitamin D intake,and VDR or TXNIP polymorphisms.This study suggests that dietary vitamin D intake is not associated with gastric cancer risk,and the genetic polymorphisms of vitamin D-related genes do not modulate the effect of vitamin D with respect to gastric carcinogenesis.展开更多
As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive ...As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring.展开更多
Type 2 diabetes(T2D) is a common metabolic disorder which is caused by multiple genetic perturbations affecting different biological pathways. Identifying genetic factors modulating the susceptibility of this complex ...Type 2 diabetes(T2D) is a common metabolic disorder which is caused by multiple genetic perturbations affecting different biological pathways. Identifying genetic factors modulating the susceptibility of this complex heterogeneous metabolic phenotype in different ethnic and racial groups remains challenging. Despite recent success, the functional role of the T2D susceptibility variants implicated by genome-wide association studies(GWAS) remains largely unknown. Genetic dissection of transcript abundance or expression quantitative trait(eQTL) analysis unravels the genomic architecture of regulatory variants. Availability of eQTL information from tissues relevant for glucose homeostasis in humans opens a new avenue to prioritize GWASimplicated variants that may be involved in triggering a causal chain of events leading to T2D. In this article, we review the progress made in the field of eQTL research and knowledge gained from those studies in understanding transcription regulatory mechanisms in human subjects. We highlight several novel approaches that can integrate eQTL analysis with multiple layers of biological information to identify ethnic-specific causal variants and gene-environment interactions relevant to T2D pathogenesis. Finally, we discuss how the eQTL analysis mediated search for "missing heritability" may lead us to novel biological and molecular mechanisms involved in susceptibility to T2D.展开更多
Objective To evaluate the association of known polymorphisms in the lipid metabolic pathway with body mass index （BMI）, and estimate their interactions with soybean food intake. Methods A community-based cross-secti...Objective To evaluate the association of known polymorphisms in the lipid metabolic pathway with body mass index （BMI）, and estimate their interactions with soybean food intake. Methods A community-based cross-sectional survey was conducted in a Chinese Han population. BMI, soybean food intake, and single nucleotide polymorphisms of rs599839, rs3846662, rs3846663, rs12916, rs174547, rs174570, rs4938303, and rs1558861 were measured in 944 subjects. A multivariate logistic regression was used to analyze the association of the studied polymorphisms with BMIs. The expectation-maximization algorithm was employed to evaluate the extent of linkage disequilibrium between pairwise polymorphisms. The gene-environment interaction was assessed in the general multifactor dimensionality reduction model. Results The polymorphisms of rs3846662 and rs3846663 were associated with 10% highest BMIs when comparing to the 10% lowest values both in individuals and haplotype-based association tests. Although no statistically significant gene-environment interactions were found, people with the haplotype composed of C allele in rs3846662 and T allele in rs3846663 and low frequency of soybean intake had significantly hisher risk to overweight and obesity as compared with those with the haplotype consisting of T allele in rs3846662 and C allele in rs3846663 and highly frequent soybean food intake, with an odds ratio of 1.64 （95% confidence interval： 1.15-2.34, P〈0.01） after adjusting for the common confounders. Conclusion Our study has sugsested that rs3846662 and rs3846663 may be the potential candidate polymorphisms for obesity, and their effect on the pathogenesis could be mediated by the frequency of soybean food intake.展开更多
Inbreeding negatively affects various life-history traits, with inbred individuals typically having lower fit- ness than outbred individuals （=inbreeding depression）. Inbreeding depression is often emphasized under ...Inbreeding negatively affects various life-history traits, with inbred individuals typically having lower fit- ness than outbred individuals （=inbreeding depression）. Inbreeding depression is often emphasized under environmental stress, but the underlying mechanisms and potential long-lasting consequences of such inbreeding-environment interactions remain poorly understood. Here, we hypothesize that inbreeding-environment interactions that occur early in life have long-term physiological effects, in partic- ular on the adult oxidative balance. We applied a unique experimental design to manipulate early life conditions of inbred and outbred songbirds （Serinus canaria） that allowed us to separate prenatal and postnatal components of early life conditions and their respective importance in inbreeding-environment interactions. We measured a wide variety of markers of oxidative status in adulthood, resulting in a com- prehensive account for oxidative balance. Using a Bayesian approach with Markov chain Monte Carlo, we found clear sex-specific effects and we also found only in females small yet significant long-term effects of inbreeding-environment interactions on adult oxidative balance. Postnatal components of early life conditions were most persuasively reflected on adult oxidative balance, with inbred females that experienced disadvantageous postnatal conditions upregulating enzymatic antioxidants in adulthood. Our study provides some evidence that adult oxidative balance can reflect inbreeding-environment inter- actions early in life, but given the rather small effects that were limited to females, we conclude that oxida- tive stress miaht have a limited role as mechanism underlvina inhre.e.dina-envirnnme.nt inte.raetinn.q_展开更多
Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system.Often associated with atrophy of the affected central or peripheral nervous structures,they include diseases such as Park...Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system.Often associated with atrophy of the affected central or peripheral nervous structures,they include diseases such as Parkinson’s Disease(PD),Alzheimer’s Disease and other dementias,Genetic Brain Disorders,Amyotrophic Lateral Sclerosis(ALS or Lou Gehrig’s Disease),Huntington’s Disease,Prion Diseases,and others.The prevalence of neurodegenerative diseases has increased over the last years.This has had a major impact both on patients and their families and has exponentially increased the medical bill by hundreds of billions of Euros.Therefore,understanding the role of environmental and genetic factors in the pathogenesis of PD is crucial to develop preventive strategies.While some authors believe that PD is mainly genetic and that the aging of the society is the principal cause for this increase,different studies suggest that PD may be due to an increased exposure to environmental toxins.In this article we review epidemiological,sociological and experimental studies to determine which hypothesis is more plausible.Our conclusion is that,at least in idiopathic PD(iPD),the exposure to toxic environmental substances could play an important role in its aetiology.展开更多
Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to ...Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn’s disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults.展开更多
Background Iron overload is frequently observed in non-alcoholic fatty liver disease(NAFLD).Transferrin receptor 2(TFR2)is an important key factor in iron regulation.We aimed to investigate whether TFR2 single nucleot...Background Iron overload is frequently observed in non-alcoholic fatty liver disease(NAFLD).Transferrin receptor 2(TFR2)is an important key factor in iron regulation.We aimed to investigate whether TFR2 single nucleotide polymorphisms(SNPs)contribute to susceptibility to NAFLD in a Chinese Han population.Methods Five tag SNPs(rs10247962,rs4434553,rs2075672,rs1052897,and rs3757859)in the TFR2 gene were selected and genotyped in a case–control study on participants who visited two affiliated hospitals of Fujian Medical University between June 2011 and August 2017.Propensity score matching and inverse probability of treatment weighting analyses were used to verify the risk associated with TFR2 SNPs.Results Logistic regression analyses suggested that subjects with the rs4434553 GA or GG genotype had a lower risk of NAFLD than those carrying the AA genotype(odds ratio=0.630,95%confidence interval=0.504–0.788).Moreover,the rs4434553 GA or GG genotype was negatively correlated with body mass index,hepatic steatosis index,and serum ferritin(b=-0.363,P=0.008;b=-1.040,P=0.009;b=-35.258,P=0.015,respectively),and positively associated with serum hepcidin level(b=35.308,P<0.001).Moreover,rs10247962 and rs1052897 had multiplicative interactions with age in relation to the risk of NAFLD(P for interactions,0.041 and 0.034,respectively).The cumulative effects of the rs10247962,rs1052897,and rs4434553 SNPs were positively associated with the risk of NAFLD(adjusted P_(trend)=0.012).Conclusions In this Chinese Han population,the rs4434553 polymorphism in TFR2 may be an independent influencing factor associated with the susceptibility to NAFLD.The ageing effect on the development of NAFLD may be inhibited by SNPs rs10247962 and rs1052897.展开更多
文摘Background The present study was undertaken to replicate the associations of representative polymorphisms in three genes （complement factor H （CFH）, complement factor B （BF） and HtrA serine peptidase 1 （HTRA1）） with exudative age-related macular degeneration （AMD） in a Han Chinese population, and to test if the modifiable environmental factors affect AMD susceptibility associated with different type of genotype in these genes. Methods An age, gender and ethnicity matched case-control study was conducted to genotype the representative single neucleotide polymorphisms （SNPs） loci including rs1061170 and rs1410996 in CFH, rs641153 and rs4151667 in BF and rs11200638 in HTRA1 gene in 144 exudative AMD patients and 126 normal controls using PCR-RFLP and direct resequencing. The demographic characteristics and behavioral risk factors were also recorded. Allelic and genotypic associations for individual SNP and joint associations with two loci were performed. The gene-gene and gene-environment interactions were analyzed using multivariate non-conditional Logistic regression analysis. Results The C risk allele frequencies for CFH Y402H （rs1061170） in cases and controls were 12.5% and 5.4% respectively, which were much lower than those in Caucasians （P 〈0.001）. Compared with TT homozygous genotype, the CT heterozygous genotype was positively associated with AMD with odds ratio （OR） of 3.23 （1.36-5.07）. However, the population attributable risk （PAR） of C allele was only 3.3% （1.4%-4.3%）. rs1410996 was also associated with AMD independent of Y402H. The ORs of exudative AMD for individuals carrying one copy risk allele and two copy risk alleles were 2.57 （1.21-5.45） and 4.76 （2.15-10.55） respectively, with correspondent PARs of 28.3% （2.0%-40.5%） and 38.2% （21.8%-45.4%）. rs11200636 in HTRA1 was another susceptible locus for AMD and the risk homozygotes were significantly susceptible for exudutive AMD （OR=3.98, 1.88-8.43） with PAR of 38.9% （24.3%-45.8%）
文摘Objective To evaluate the effects of environmental factors and microRNAs （miRNAs） （miR-126, miR-143, and miR-145） on the risk of coronary heart disease （CHD）. Methods A frequency-matched case-control study （450 patients, 450 controls） was conducted from April 2014 to December 2016 in Fuzhou City, China. Environmental factors were investigated using a self-administered questionnaire, and the expression levels of miR-126, rniR-143, and miR-145 were determined by quantitative real-time Polymerase Chain Reaction （PCR） in pe- ripheral blood mononuclear cells. Unconditional logistic regression models were used for statistical evaluation. Results Alcohol consumption, high-salt diets, high-intensity work, and lack of physical activity were significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. MiR-126, miR-143, and miR-145 were highly expressed in the CHD group compared with the control group. After adjustment for other environmental factors, unconditional logistic regression results revealed that miR-126, miR-143, and depression were the independent risk factors of CHD, and light diet was the independent protective factor of CHD. Conclusions Our data suggest that a family history of CHD, anxiety, and alcohol consumption was significantly associated with increased CHD risk, whereas light diet was significantly associated with decreased risk. Furthermore, miR-126 and miR-143 in combination with several risk factors, could play a joint role in the development of CHD. Therefore, it is necessary to manage patients with CHD in all directions and multiple level.
文摘Inflammation plays a significant role in the etiology of type 2 diabetes mellitus(T2DM).The rise in the pro-inflammatory cytokines is the essential step in glucotoxicity and lipotoxicity induced mitochondrial injury,oxidative stress and beta cell apoptosis in T2 DM.Among the recognized markers are interleukin(IL)-6,IL-1,IL-10,IL-18,tissue necrosis factor-alpha(TNF-α),C-reactive protein,resistin,adiponectin,tissue plasminogen activator,fibrinogen and heptoglobins.Diabetes mellitus has firm genetic and very strong environmental influence; exhibiting a polygenic mode of inheritance.Many single nucleotide polymorphisms(SNPs) in various genes including those of pro and antiinflammatory cytokines have been reported as a risk for T2 DM.Not all the SNPs have been confirmed by unifying results in different studies and wide variations have been reported in various ethnic groups.The inter-ethnic variations can be explained by the fact that gene expression may be regulated by gene-gene,gene-environment and gene-nutrient interactions.This review highlights the impact of these interactions on determining the role of single nucleotide polymorphism of IL-6,TNF-α,resistin and adiponectin in pathogenesis of T2 DM.
文摘AIM: To examine the effect of the potential interaction between KIF1 B variants(rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma(HCC) in a high-risk region in China.METHODS: Three hundred and six patients with HCC and 306 hospital-based control participants residing in the Shunde region of Guangdong Province, China were enrolled. Clinical characteristics were collected by reviewing the complete medical histories from the patient archives, and epidemiological data were collected using a questionnaire and clinical examination. Two single nucleotide polymorphisms(SNPs) of KIF1B(rs17401966 and rs3748578) were chosen for the current study. All subjects were genotypedusing a Taq Man real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions.RESULTS: Smoking, frequent consumption of raw freshwater fish, hepatitis B virus(HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio(OR) = 12.02; 95% confidence interval(95%CI): 6.02-24.00]. No significant association was found between the KIF1 B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption(P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC(OR = 2.36; 95%CI: 1.49-3.74).CONCLUSION: The gene-environment interaction between the KIF1 B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.
文摘BACKGROUND Autism spectrum disorder(ASD)is a complex neurodevelopmental condition characterized by heterogeneous symptoms and genetic underpinnings.Recent advancements in genetic and epigenetic research have provided insights into the intricate mechanisms contributing to ASD,influencing both diagnosis and therapeutic strategies.AIM To explore the genetic architecture of ASD,elucidate mechanistic insights into genetic mutations,and examine gene-environment interactions.METHODS A comprehensive systematic review was conducted,integrating findings from studies on genetic variations,epigenetic mechanisms(such as DNA methylation and histone modifications),and emerging technologies[including Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR)-Cas9 and single-cell RNA sequencing].Relevant articles were identified through systematic searches of databases such as PubMed and Google Scholar.RESULTS Genetic studies have identified numerous risk genes and mutations associated with ASD,yet many cases remain unexplained by known factors,suggesting undiscovered genetic components.Mechanistic insights into how these genetic mutations impact neural development and brain connectivity are still evolving.Epigenetic modifications,particularly DNA methylation and non-coding RNAs,also play significant roles in ASD pathogenesis.Emerging technologies like CRISPR-Cas9 and advanced bioinformatics are advancing our understanding by enabling precise genetic editing and analysis of complex genomic data.CONCLUSION Continued research into the genetic and epigenetic underpinnings of ASD is crucial for developing personalized and effective treatments.Collaborative efforts integrating multidisciplinary expertise and international collaborations are essential to address the complexity of ASD and translate genetic discoveries into clinical practice.Addressing unresolved questions and ethical considerations surrounding genetic research will pave the way for improved diagnostic tools and targeted therapies,ultimately enhancing outcomes for
基金This work was supported by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health(NINDS R03 NS09324501A1 and NINDS/NIH 1R21NS087235-01A1 to to X.G.).
文摘Evidence from epidemiological studies suggest a relationship between cigarette smoking and low risk of Parkinson disease(PD).As a major component of tobacco smoke,nicotine has been proposed to be a substance for preventing against PD risk,with a key role in regulating striatal activity and behaviors mediated through the dopaminergic system.Animal studies also showed that nicotine could modulate dopamine transmission and reduce levodopa-induced dyskinesias.However,previous clinical trials yield controversial results regarding nicotine treatment.In this review,we updated epidemiological,preclinical and clinical data,and studies on nicotine from diet.We also reviewed interactions between genetic factors and cigarette smoking.As a small amount of nicotine can saturate a substantial portion of nicotine receptors in the brain,nicotine from other sources,such as diet,could be a promising therapeutic substance for protection against PD.
基金supported by grants from the National Natural Science Foundation of China(Nos.91846303 and 81941018)The CKB baseline survey and the first re-survey were supported by a grant from the Kadoorie Charitable Foundation in Hong Kong,China.The long-term follow-up is supported by grants(Nos.2016YFC0900500,2016YFC0900501,and 2016YFC0900504)+3 种基金from the National Key Research and Development Program of China,and Chinese Ministry of Science and Technology(No.2011BAI09B01)Dr.Pang acknowledged support from the China Postdoctoral Science Foundation(Nos.2019TQ0008 and 2020M670071)the Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological Innovation(No.BMU2022 RCZX022)the Fundamental Research Funds for the Central Universities,and the Peking University Start-up Grant(No.BMU2022PY014)
文摘Background:Severe liver disease(SLD),including cirrhosis and liver cancer,constitutes a major disease burden in China.We aimed to examine the association of genetic and healthy lifestyle factors with the incidence and prognosis of SLD.Methods:The study population included 504,009 participants from the prospective China Kadoorie Biobank aged 30-79 years.The individuals were from 10 diverse areas in China without a history of cancer or liver disease at baseline.Cox regression was used to estimate adjusted hazard ratios(HRs)for incident SLD and death after SLD diagnosis associated with healthy lifestyle factors(smoking,alcohol,physical activity,and central adiposity).Additionally,the contribution of genetic risk for hepatitis B virus(HBV,assessed by genetic variants in major histocompatibility complex,class II,DP/DQ[HLA-DP/DQ]genes)was also estimated.Results:Compared with those with 0-1 healthy lifestyle factor,participants with 2,3,and 4 factors had 12%(HR 0.88[95%confidence interval[CI]0.85,0.92]),26%(HR 0.74[95%CI:0.69,0.79]),and 44%(HR 0.56[95%CI:0.48,0.65])lower risks of SLD,respectively.Inverse associations were observed among participants with both low and high genetic risks(HR per 1-point increase 0.83[95%CI:0.74,0.94]and 0.91[95%CI:0.82,1.02],respectively;P_(interaction)=0.51),although with a non-significant trend among those with a high genetic risk.Inverse associations were also observed between healthy lifestyle factors and liver biomarkers regardless of the genetic risk.Despite the limited power,healthy lifestyle factors were associated with a lower risk of death after incident SLD among participants with a low genetic risk(HR 0.59[95%CI:0.37,0.96]).Conclusions:Lifestyle modification may be beneficial in terms of lowering the risk of SLD regardless of the genetic risk.Moreover,it is also important for improving the prognosis of SLD in individuals with a low genetic risk.Future studies are warranted to examine the impact of healthy lifestyles on SLD prognosis,particularly among individuals with a high ge
基金supported by the Agriculture and Food Research Initiative competitive grant(2021-67013-33833)the USDA National Institute of Food and Agriculture,the Advanced Research Projects Agency-Energy program(DEAR0000826)+1 种基金the Department of Energy,the National Science Foundation(IOS-1546657)the Iowa State University Ray-mond F.Baker Center for Plant Breeding,and the Iowa State University Plant Sciences Institute.
文摘Identifying mechanisms and pathways involved in gene–environment interplay and phenotypic plasticity is a long-standing challenge.It is highly desirable to establish an integrated framework with an environmental dimension for complex trait dissection and prediction.A critical step is to identify an environmental index that is both biologically relevant and estimable for new environments.With extensive field-observed complex traits,environmental profiles,and genome-wide single nucleotide polymorphisms for three major crops(maize,wheat,and oat),we demonstrated that identifying such an environmental index(i.e.,a combination of environmental parameter and growth window)enables genome-wide association studies and genomic selection of complex traits to be conducted with an explicit environmental dimension.Interestingly,genes identified for two reaction-norm parameters(i.e.,intercept and slope)derived from flowering time values along the environmental index were less colocalized for a diverse maize panel than for wheat and oat breeding panels,agreeing with the different diversity levels and genetic constitutions of the panels.In addition,we showcased the usefulness of this framework for systematically forecasting the performance of diverse germplasm panels in new environments.This general framework and the companion CERIS-JGRA analytical package should facilitate biologically informed dissection of complex traits,enhanced performance prediction in breeding for future climates,and coordinated efforts to enrich our understanding of mechanisms underlying phenotypic variation.
基金supported by the National Research Foundation of Korea Grantfunded by the Korean Government(Ministry of Education,Science and Technology)[NRF-355-2010-1-E00026 and 2012R1-A1A2044765]
文摘There have been few studies on the association between vitamin D levels and gastric cancer in Asian populations,but no studies have been performed on the interactions between vitamin D intake and polymorphisms in the vitamin D pathway.The effects of vitamin D intake,vitamin D related genetic polymorphisms,and their association with the incidence of gastric cancer were investigated in a hospital case-control study,including 715 pairs of newly diagnosed gastric cancer patients and controls matched for age and sex.Correlations between vitamin D intake and plasma vitamin D concentrations were also assessed in a subset of subjects.No statistically significant difference was observed in the dietary intake of vitamin D between the patients and controls,nor were there any evident associations between vitamin D intake and risk of gastric cancer in multivariate analyses.Vitamin D intake significantly correlated with the circulating 25-hydroxyvitamin D levels,but not with the active form of the vitamin,1,25-dihydroxyvitamin D.There were no statistically significant interactions between vitamin D intake,and VDR or TXNIP polymorphisms.This study suggests that dietary vitamin D intake is not associated with gastric cancer risk,and the genetic polymorphisms of vitamin D-related genes do not modulate the effect of vitamin D with respect to gastric carcinogenesis.
文摘As genetic factors can hardly explain the changes taking place during short time spans, environmental and lifestyle-related factors have been suggested as the causes of time-related deterioration of male reproductive function. However, considering the strong heterogeneity of male fecundity between and within populations, genetic variants might be important determinants of the individual susceptibility to the adverse effects of environment or lifestyle. Although the possible mechanisms of such interplay in relation to the reproductive system are largely unknown, some recent studies have indicated that specific genotypes may confer a larger risk of male reproductive disorders following certain exposures. This paper presents a critical review of animal and human evidence on how genes may modify environmental effects on male reproductive function. Some examples have been found that support this mechanism, but the number of studies is still limited. This type of interaction studies may improve our understanding of normal physiology and help us to identify the risk factors to male reproductive malfunction. We also shortly discuss other aspects of gene-environment interaction specifically associated with the issue of reproduction, namely environmental and lifestyle factors as the cause of sperm DNA damage. It remains to be investigated to what extent such genetic changes, by natural conception or through the use of assisted reproductive techniques, are transmitted to the next generation, thereby causing increased morbidity in the offspring.
基金Supported by National Institutes of Health(NIH/NIDDK),Nos.R01 DK090111 and DK039311
文摘Type 2 diabetes(T2D) is a common metabolic disorder which is caused by multiple genetic perturbations affecting different biological pathways. Identifying genetic factors modulating the susceptibility of this complex heterogeneous metabolic phenotype in different ethnic and racial groups remains challenging. Despite recent success, the functional role of the T2D susceptibility variants implicated by genome-wide association studies(GWAS) remains largely unknown. Genetic dissection of transcript abundance or expression quantitative trait(eQTL) analysis unravels the genomic architecture of regulatory variants. Availability of eQTL information from tissues relevant for glucose homeostasis in humans opens a new avenue to prioritize GWASimplicated variants that may be involved in triggering a causal chain of events leading to T2D. In this article, we review the progress made in the field of eQTL research and knowledge gained from those studies in understanding transcription regulatory mechanisms in human subjects. We highlight several novel approaches that can integrate eQTL analysis with multiple layers of biological information to identify ethnic-specific causal variants and gene-environment interactions relevant to T2D pathogenesis. Finally, we discuss how the eQTL analysis mediated search for "missing heritability" may lead us to novel biological and molecular mechanisms involved in susceptibility to T2D.
基金supported by the National Basic Research Program of China(973 Program)(2006CB503903)the National Natural Science Foundation of China(81172744,81230066)
文摘Objective To evaluate the association of known polymorphisms in the lipid metabolic pathway with body mass index （BMI）, and estimate their interactions with soybean food intake. Methods A community-based cross-sectional survey was conducted in a Chinese Han population. BMI, soybean food intake, and single nucleotide polymorphisms of rs599839, rs3846662, rs3846663, rs12916, rs174547, rs174570, rs4938303, and rs1558861 were measured in 944 subjects. A multivariate logistic regression was used to analyze the association of the studied polymorphisms with BMIs. The expectation-maximization algorithm was employed to evaluate the extent of linkage disequilibrium between pairwise polymorphisms. The gene-environment interaction was assessed in the general multifactor dimensionality reduction model. Results The polymorphisms of rs3846662 and rs3846663 were associated with 10% highest BMIs when comparing to the 10% lowest values both in individuals and haplotype-based association tests. Although no statistically significant gene-environment interactions were found, people with the haplotype composed of C allele in rs3846662 and T allele in rs3846663 and low frequency of soybean intake had significantly hisher risk to overweight and obesity as compared with those with the haplotype consisting of T allele in rs3846662 and C allele in rs3846663 and highly frequent soybean food intake, with an odds ratio of 1.64 （95% confidence interval： 1.15-2.34, P〈0.01） after adjusting for the common confounders. Conclusion Our study has sugsested that rs3846662 and rs3846663 may be the potential candidate polymorphisms for obesity, and their effect on the pathogenesis could be mediated by the frequency of soybean food intake.
文摘Inbreeding negatively affects various life-history traits, with inbred individuals typically having lower fit- ness than outbred individuals （=inbreeding depression）. Inbreeding depression is often emphasized under environmental stress, but the underlying mechanisms and potential long-lasting consequences of such inbreeding-environment interactions remain poorly understood. Here, we hypothesize that inbreeding-environment interactions that occur early in life have long-term physiological effects, in partic- ular on the adult oxidative balance. We applied a unique experimental design to manipulate early life conditions of inbred and outbred songbirds （Serinus canaria） that allowed us to separate prenatal and postnatal components of early life conditions and their respective importance in inbreeding-environment interactions. We measured a wide variety of markers of oxidative status in adulthood, resulting in a com- prehensive account for oxidative balance. Using a Bayesian approach with Markov chain Monte Carlo, we found clear sex-specific effects and we also found only in females small yet significant long-term effects of inbreeding-environment interactions on adult oxidative balance. Postnatal components of early life conditions were most persuasively reflected on adult oxidative balance, with inbred females that experienced disadvantageous postnatal conditions upregulating enzymatic antioxidants in adulthood. Our study provides some evidence that adult oxidative balance can reflect inbreeding-environment inter- actions early in life, but given the rather small effects that were limited to females, we conclude that oxida- tive stress miaht have a limited role as mechanism underlvina inhre.e.dina-envirnnme.nt inte.raetinn.q_
文摘Neurodegenerative diseases are characterized by a progressive dysfunction of the nervous system.Often associated with atrophy of the affected central or peripheral nervous structures,they include diseases such as Parkinson’s Disease(PD),Alzheimer’s Disease and other dementias,Genetic Brain Disorders,Amyotrophic Lateral Sclerosis(ALS or Lou Gehrig’s Disease),Huntington’s Disease,Prion Diseases,and others.The prevalence of neurodegenerative diseases has increased over the last years.This has had a major impact both on patients and their families and has exponentially increased the medical bill by hundreds of billions of Euros.Therefore,understanding the role of environmental and genetic factors in the pathogenesis of PD is crucial to develop preventive strategies.While some authors believe that PD is mainly genetic and that the aging of the society is the principal cause for this increase,different studies suggest that PD may be due to an increased exposure to environmental toxins.In this article we review epidemiological,sociological and experimental studies to determine which hypothesis is more plausible.Our conclusion is that,at least in idiopathic PD(iPD),the exposure to toxic environmental substances could play an important role in its aetiology.
基金Supported by Grants from"Fondo de Investigaciones Sanitarias",PI11/00614"Fundación Eugenio Rodríguez Pascual"
文摘Recent findings demonstrate the common genetic basis for many immune-mediated diseases, and consequently, the partially shared pathogenesis. We collected these findings and reviewed the extension of these overlaps to other disease characteristics. Two autoimmune diseases were selected that also share the specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, inflammatory bowel disease (IBD) and celiac disease (CeD), are not completely understood. Both are complex diseases with genetics and environment contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. CeD constitutes a particular disease because the main environmental and genetic triggers are largely known. IBD comprises two main clinical forms, Crohn’s disease and ulcerative colitis, which most likely involve a complex interplay between some components of the commensal microbiota and other environmental factors in their origin. These multifactorial diseases encompass a broad spectrum of clinical phenotypes and ages of onset, although the clinical presentation often differs depending on childhood or adult onset, with greater heterogeneity commonly observed in adults.
基金supported by the National Natural Science Foundation of China[grant number 81473047]the Natural Science Foundation of Fujian Province[grant number 2019J01316].
文摘Background Iron overload is frequently observed in non-alcoholic fatty liver disease(NAFLD).Transferrin receptor 2(TFR2)is an important key factor in iron regulation.We aimed to investigate whether TFR2 single nucleotide polymorphisms(SNPs)contribute to susceptibility to NAFLD in a Chinese Han population.Methods Five tag SNPs(rs10247962,rs4434553,rs2075672,rs1052897,and rs3757859)in the TFR2 gene were selected and genotyped in a case–control study on participants who visited two affiliated hospitals of Fujian Medical University between June 2011 and August 2017.Propensity score matching and inverse probability of treatment weighting analyses were used to verify the risk associated with TFR2 SNPs.Results Logistic regression analyses suggested that subjects with the rs4434553 GA or GG genotype had a lower risk of NAFLD than those carrying the AA genotype(odds ratio=0.630,95%confidence interval=0.504–0.788).Moreover,the rs4434553 GA or GG genotype was negatively correlated with body mass index,hepatic steatosis index,and serum ferritin(b=-0.363,P=0.008;b=-1.040,P=0.009;b=-35.258,P=0.015,respectively),and positively associated with serum hepcidin level(b=35.308,P<0.001).Moreover,rs10247962 and rs1052897 had multiplicative interactions with age in relation to the risk of NAFLD(P for interactions,0.041 and 0.034,respectively).The cumulative effects of the rs10247962,rs1052897,and rs4434553 SNPs were positively associated with the risk of NAFLD(adjusted P_(trend)=0.012).Conclusions In this Chinese Han population,the rs4434553 polymorphism in TFR2 may be an independent influencing factor associated with the susceptibility to NAFLD.The ageing effect on the development of NAFLD may be inhibited by SNPs rs10247962 and rs1052897.
