Green Revolution made a substantial contribution to wheat yields worldwide in the 196os and 197os. It is of great importance to analyze the haplotype variation of Rht-D1, the Green Revolution gene, during wheat （Trit...Green Revolution made a substantial contribution to wheat yields worldwide in the 196os and 197os. It is of great importance to analyze the haplotype variation of Rht-D1, the Green Revolution gene, during wheat （Triticum aestivum L.） domestication and breeding to understand its evolution and function in wheat breeding history. In this study, the Rht-D1 and its flanking regions were sequenced and single nucleotide polymorphisms were detected based on a panel of 45 accessions of Aegilops tauschii, 51 accessions of landraces and 8o accessions of commercial varieties. Genetic diversity in the wild accessions was much higher than that in the varieties and higher than that reported previously. Seven haplotypes （Hapl I to Hapl VII） of Rht-D1 were identified and their evolutionary relationships were proposed. In addition to the well-known Green Revolution allele Rht-Dlb, Hapl Vii （an allele Rht-Dlk） was identified in early breeding varieties, whichreduced plant height by 16%. The results suggested that Rht-Dlk had been used in breeding before the Green Revolution and made a great contribution to wheat production worldwide. Based on the breeding history and molecular evidence, we proposed that the wheat Green Revolution in China and International Maize and Wheat Improvement Center （CIMMYT） occurred independently.展开更多
KCNQ1 has been identified as a susceptibility gene of type 2 diabetes mellitus （T2DM） in Asian populations through genome-wide association studies. However, studies on the association between gene polymorphism of KC...KCNQ1 has been identified as a susceptibility gene of type 2 diabetes mellitus （T2DM） in Asian populations through genome-wide association studies. However, studies on the association between gene polymorphism of KCNQ1 and T2DM complications remain unclear. To further ana- lyze the association between different alleles at the single nncleotide polymorphism （SNP） rs2237892 within KCNQ1 and TD2M and its complications, we conducted a case-control study in a Chinese Han population. The C allele of rs2237892 variant contributed to susceptibility to T2DM （odds ratio [OR], 1.45; 95% confidence interval [CI], 1.20 1.75）. Genotypes CT （OR, 1.97; 95% CI, 1.24-3.15） and CC （OR, 2.49; 95% CI, 1.57-3.95） were associated with an increased risk of T2DM. Multivariate regression analysis was performed with adjustment of age, gender, and body mass index. We found that systolic blood pressure （P = 0.015）, prevalence of hypertension （P = 0.037）, and risk of maerovascnlar disease （OR, 2.10; CI, 1.00-4.45） were significantly higher in subjects with the CC genotype than in the combined population with genotype either CT or TT. Therefore, our data support that KCNQ1 might contribute to the higher incidence of patients with T2DM carrying the risk allele C population. is associated with an increased risk for T2DM and hypertension and macrovascular complications in though it needs further to be confirmed in a larger展开更多
The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder. Consequently, the norepinephrine transporter gene is an attractive candidate in...The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder. Consequently, the norepinephrine transporter gene is an attractive candidate in major depressive disorder research. In the present study, we evaluated the depression symptoms of subjects with major depressive disorder, who were all from the North of China and of Hart Chinese origin, using the Hamilton Depression Scale. We examined the relationship between two single nucleotide polymorphisms in the norepinephrine transporter, rs2242446 and rs5569, and the retardation symptoms of major depressive disorder using quantitative trait testing with the UNPHASED program, rs5569 was associated with depressed mood, and the GG genotype may be a risk factor for this; rs2242446 was associated with work and interest, and the TT genotype may be a risk factor for loss of interest. Our findings suggest that rs2242446 and rs5569 in the norepinephrine transporter gene are associated with the retardation symptoms of depression in the Hart Chinese population.展开更多
Although molecular mechanisms of heat stroke under physiological and pathological conditions have not yet been elucidated, a novel disease-associated gene encoding a calcium-binding protein, calsequestrin-1 （CASQ1）,...Although molecular mechanisms of heat stroke under physiological and pathological conditions have not yet been elucidated, a novel disease-associated gene encoding a calcium-binding protein, calsequestrin-1 （CASQ1）, was suggested relevant based on results from a transgenic murine model. Here, we show the association between single nucleotide polymorphisms （SNPs） of CASQ1 and physiological parameters for heat stroke from a study involving 150 patients. Pooled DNA from heat stroke patients were subjected to sequencing and 3 SNPs were identified. Genotypes were assigned for all patients according to g. 175A 〉 G, one SNP which leads to a nonsynonymous sub- stitution （N59D） in the first exon of human CASQ1 gene. We analyzed the genotypic data with a linear model based on significance scores between SNP （175A 〉 G） and heat stroke parameters. As a result, we found a significant association between SNP A175G and heat stroke （P ~ 0.05）. Further bioinformatics analysis of the 1-Mb flanking sequence revealed the presence of two genes that encode DDB1 and CUL4 associated factor 8 （DCAF8）, and peroxisomal biogenesis factor 19 （PEX19）, respectively, which might be functionally related to CASQ1. Our results showed that the blood calcium of patients with allele D increased significantly, compared to patients with allele N （P 〈 0.05）, which may result from the decreased calcium in muscle, suggesting that N59D in CASQ1 might account for the dysfunction of CASQ1 in calcium regulation during heat stroke.展开更多
To investigate the distribution characteristics and linkage disequilibrium of T cell immunoglobulin domain and mucin domain protein 4 （TIM4） promoter polymorphisms in asthma patients of Chinese Han population, the p...To investigate the distribution characteristics and linkage disequilibrium of T cell immunoglobulin domain and mucin domain protein 4 （TIM4） promoter polymorphisms in asthma patients of Chinese Han population, the promoter region of TIM4 was re-sequenced by PCR-sequencing, and linkage disequilibrium was analyzed by SHEsis software. Four single nucleotide polymor- phisms （SNPs） in the promoter region of TIM4 were detected, including two new SNPs （at positions -1609, -153） and two reported SNPs （rs6874202, rs6882076）. The frequency distribution of rs6882076 was different among different races （P〈0.05）. In addition, linkage disequilibrium among the SNPs of the promoter region of TIM4 was found and GGTG was the predominant haplotype. There were four SNPs in the promoter region of TIM4 in asthma patients of Chinese Han population, which were in linkage disequilibrium.展开更多
Isothermal methods, such as helicase-dependent amplification （HDA）, have an advantage over polymerase chain reaction for DNA amplification owing to their ease of operation. Here, we developed a new HDA method that i...Isothermal methods, such as helicase-dependent amplification （HDA）, have an advantage over polymerase chain reaction for DNA amplification owing to their ease of operation. Here, we developed a new HDA method that is nanoparticle-assisted, termed nanoHDA. This method uses gold nanoparticles （AuNPs） to improve the sensitivity and specificity of the isothermal method. In HDA, the denaturation of DNA templates is mediated by helicases, but this method is limited by the low denaturation efficiency of helicases. In this report, AuNPs with preferential affinity for single-stranded DNA （ssDNA） were utilized to improve the denaturation efficiency of helicases. The same affinity property of nanoparticles can also enhance specificity by suppressing primer-dimer formation. This nanoHDA method was employed to genotype the KRAS gene in genomic DNA samples from colorectal cancer patients, as achieved by the hybridization of nanoHDA amplicons using the NanoBioArray chip.展开更多
AIM： To investigate the correlation between C/T single nucleotide polymorphism （SNP） in the promoter of the DNA methyltransferase 3B （D/VMT3B） gene and risk for development and progression of primary hepatocellul...AIM： To investigate the correlation between C/T single nucleotide polymorphism （SNP） in the promoter of the DNA methyltransferase 3B （D/VMT3B） gene and risk for development and progression of primary hepatocellular carcinoma （HCC）. METHODS： One hundred case subjects were selected consecutively from Tongji Hospital （Wuhan, China）. from March to November 2006. They did not receive radiotherapy or chemotherapy for newly diagnosed and histopathologically confirmed HCC. One hundred and forty control subjects having no history of cancerous or genetic diseases were healthy volunteers to Wuhan Blood Center in the same period. Frequency was matched for sex, age, alcohol consumption and cigarette smoking status of the case subjects. C/T polymorphism of the DNMT3B promoter was analyzed using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and sequencing analysis. The association between genotypes of DNMT3B and clinicopathological parameters among cases was also studied. RESULTS： The CC genotype HCC patients and controls. was not detected in both In control subjects, the frequency of TT and CT genotypes was 99.3% and 0.7% respectively, and that of T and C alleles was 99.6% and 0.4% respectively. The frequency of CT genotype was higher in HCC （3.0%）. The frequency of T and C alleles was 98.5% and 1.5% respectively. However, the genotype and allelotype distribution in HCC patients was not significantly different from that in controls. CONCLUSION： C/T polymorphism is not associated with the increased risk of HCC. DNMT3B genetic polymorphism is variable in different races, ethnic groups or geographic areas. Further study is needed to clarify the role of DNMT3B SNP in the development of HCCamong other populations.展开更多
The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by l...The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (SNPs) and determine the correlation of these changes with serum PSA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PSA determinations were done using ELISA technique while genetic studies were carried out using real-time PCR. tPSA, fPSA, and % fPSA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPSA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPSA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed SNPs with a mean tPSA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without SNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 SNPs. Ten subjects are curated in SNP database while one is uncurated. The Chi-square test showed significant association (p = 0.00) between tPSA levels and SNPs mutation (X<sup>2</sup> = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the SNP mutations had no effect on PSA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two SNPs: rs6072 and rs74478031 were associated with elevated PSA levels (p < 0.05). Their presence, therefore, has the potential to serve, in conjunction with raised PSA, as biomarkers of prostate cancer in the study population.展开更多
Neoplastic progression is generally characterized by the accumulation of multiple genetic alterations including loss of tumor suppression gene function. Loss of heterozygosity （LOH） has been used to identify genomic...Neoplastic progression is generally characterized by the accumulation of multiple genetic alterations including loss of tumor suppression gene function. Loss of heterozygosity （LOH） has been used to identify genomic regions that harbor tumor suppressor genes and to characterize different tumor types, pathological stages and progression. LOH pattern has been detected by allelotyping using restriction fragment length polymorphism, and later by simple sequence length polymorphisms （SSLPs or microsatellite） for 10 years. This paper reviews the detection of LOH by recently developed single nucleotide polymorphism （SNP） arrays （all analyzed by Affymetrix array）; furthermore, its advantage and disadvantage were analyzed in several kinds of cancer.展开更多
AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetu...AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetuximab.METHODS: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase release.RESULTS: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment.CONCLUSION: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.展开更多
Here, we report a method that uses gold nanoparticles （AuNPs） to enhance the specificity of DNA hybridization without reducing its detection sensitivity. The conventional stringent wash method utilizes high-temperat...Here, we report a method that uses gold nanoparticles （AuNPs） to enhance the specificity of DNA hybridization without reducing its detection sensitivity. The conventional stringent wash method utilizes high-temperatureflow-salt conditions to enhance the specificity of DNA hybridization-based assays. This method creates a destabilizing environment for base pairing that affects specific and nonspecific duplexes. Therefore, specificity is achieved at the expense of signal intensity or sensitivity. However, in the proposed wash method, AuNPs predominantly destabilize nonspecific duplexes, offering specificity without compromising sensitivity. This AuNP wash technique has proven to be effective in detecting single nucleotide polymorphisms （SNPs） in genomic samples even at room temperature in a CD-like NanoBioArray （CD-NBA） chip. This method is also robust with sequence variation and is compatible with multiplex DNA analyses on microarrays. Thus, the AuNP wash method could potentially be useful for improving the accuracy of DNA hybridization results.展开更多
AIM:To evaluate the relationship between apurinic endonuclease 1(APE1) Asp148 Glu polymorphism and the susceptibility to gastrointestinal(GI) cancers.METHODS:We searched Pub Med, ISI Web of Knowledge, and Chinese Nati...AIM:To evaluate the relationship between apurinic endonuclease 1(APE1) Asp148 Glu polymorphism and the susceptibility to gastrointestinal(GI) cancers.METHODS:We searched Pub Med, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure(CNKI) databases updated on July 15, 2014 for relevant studies.Only case-control studies comparing APE1 Asp148 Glu polymorphism and GI cancer risk were included.We excluded studies reporting only standardized incidence ratios without control groups and those without detailed genotyping data.Meta-analysis was performed on 17 studies involving 4856 cancer patients and 6136 cancer-free controls.Review Manager version 5.1 was used to perform the meta-analysis.The pooled odds ratios(ORs) and 95% confidence intervals(CIs) were estimated under the allele contrast, homozygous, heterozygous, dominant and recessive genetic models.We also conducted subgroup analyses stratified by ethnicity and cancer type.Publication bias was evaluated using Begg's test.RESULTS:The meta-analysis showed a significant association between APE1 Asp148Glu polymorphism and GI cancer risk in three genetic models in the overall population(G vs T:OR=1.18;95%CI:1.05-1.32;TG vs TT:OR=1.28;95%CI:1.08-1.52;TG+GG vs TT:OR=1.32;95%CI:1.10-1.57).Stratified analysis by ethnicity revealed a statistically increased GI cancer risk in Asians(G vs T:OR=1.27;95%CI:1.07-1.51;GG vs TT:OR=1.58;95%CI:1.05-2.38;TG vs TT:OR=1.30;95%CI,1.01-1.67;and TG+GG vs TT:OR=1.38;95%CI:1.07-1.78),but not in Caucasians.Furthersubgroup analysis by cancer type indicated that APE1Asp148Glu polymorphism may contribute to gastric cancer risk.However,Asp148Glu has no significant association with colorectal or esophageal cancer risk in any genetic model.CONCLUSION:This meta-analysis suggests that the APE1 Asp148Glu polymorphism G allele is associated with an increased GI cancer risk,especially in gastric cancer.展开更多
基金supported by the National Basic Research Program of China (2010CB125905, 2010CB951501)National Transgenic Major Project (2013 08009-001)
文摘Green Revolution made a substantial contribution to wheat yields worldwide in the 196os and 197os. It is of great importance to analyze the haplotype variation of Rht-D1, the Green Revolution gene, during wheat （Triticum aestivum L.） domestication and breeding to understand its evolution and function in wheat breeding history. In this study, the Rht-D1 and its flanking regions were sequenced and single nucleotide polymorphisms were detected based on a panel of 45 accessions of Aegilops tauschii, 51 accessions of landraces and 8o accessions of commercial varieties. Genetic diversity in the wild accessions was much higher than that in the varieties and higher than that reported previously. Seven haplotypes （Hapl I to Hapl VII） of Rht-D1 were identified and their evolutionary relationships were proposed. In addition to the well-known Green Revolution allele Rht-Dlb, Hapl Vii （an allele Rht-Dlk） was identified in early breeding varieties, whichreduced plant height by 16%. The results suggested that Rht-Dlk had been used in breeding before the Green Revolution and made a great contribution to wheat production worldwide. Based on the breeding history and molecular evidence, we proposed that the wheat Green Revolution in China and International Maize and Wheat Improvement Center （CIMMYT） occurred independently.
基金supported by the National Natural Science Foundation of China(Grant No. 81271918)Zhejiang Provincial Natural Science Foundation of China (Grant No. Y2090753)+2 种基金Key Science and Technology Innovation Team of Zhejiang Province (Grant No. 2010R50048)Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talentsthe Medical Scientific Projects from the Health Bureau of Zhejiang Province (Grant No. 2011ZDA016)
文摘KCNQ1 has been identified as a susceptibility gene of type 2 diabetes mellitus （T2DM） in Asian populations through genome-wide association studies. However, studies on the association between gene polymorphism of KCNQ1 and T2DM complications remain unclear. To further ana- lyze the association between different alleles at the single nncleotide polymorphism （SNP） rs2237892 within KCNQ1 and TD2M and its complications, we conducted a case-control study in a Chinese Han population. The C allele of rs2237892 variant contributed to susceptibility to T2DM （odds ratio [OR], 1.45; 95% confidence interval [CI], 1.20 1.75）. Genotypes CT （OR, 1.97; 95% CI, 1.24-3.15） and CC （OR, 2.49; 95% CI, 1.57-3.95） were associated with an increased risk of T2DM. Multivariate regression analysis was performed with adjustment of age, gender, and body mass index. We found that systolic blood pressure （P = 0.015）, prevalence of hypertension （P = 0.037）, and risk of maerovascnlar disease （OR, 2.10; CI, 1.00-4.45） were significantly higher in subjects with the CC genotype than in the combined population with genotype either CT or TT. Therefore, our data support that KCNQ1 might contribute to the higher incidence of patients with T2DM carrying the risk allele C population. is associated with an increased risk for T2DM and hypertension and macrovascular complications in though it needs further to be confirmed in a larger
基金supported by the National Natural Science Foundation of China,No. 30770770,30971054,and81171290Science Foundation for the Youth of Shanxi,No.2011021036-1
文摘The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder. Consequently, the norepinephrine transporter gene is an attractive candidate in major depressive disorder research. In the present study, we evaluated the depression symptoms of subjects with major depressive disorder, who were all from the North of China and of Hart Chinese origin, using the Hamilton Depression Scale. We examined the relationship between two single nucleotide polymorphisms in the norepinephrine transporter, rs2242446 and rs5569, and the retardation symptoms of major depressive disorder using quantitative trait testing with the UNPHASED program, rs5569 was associated with depressed mood, and the GG genotype may be a risk factor for this; rs2242446 was associated with work and interest, and the TT genotype may be a risk factor for loss of interest. Our findings suggest that rs2242446 and rs5569 in the norepinephrine transporter gene are associated with the retardation symptoms of depression in the Hart Chinese population.
基金support from the Department of Emergency of Beijing Electric Power Hospitalthe Department of Molecular Biology of Chinese PLA Medical School
文摘Although molecular mechanisms of heat stroke under physiological and pathological conditions have not yet been elucidated, a novel disease-associated gene encoding a calcium-binding protein, calsequestrin-1 （CASQ1）, was suggested relevant based on results from a transgenic murine model. Here, we show the association between single nucleotide polymorphisms （SNPs） of CASQ1 and physiological parameters for heat stroke from a study involving 150 patients. Pooled DNA from heat stroke patients were subjected to sequencing and 3 SNPs were identified. Genotypes were assigned for all patients according to g. 175A 〉 G, one SNP which leads to a nonsynonymous sub- stitution （N59D） in the first exon of human CASQ1 gene. We analyzed the genotypic data with a linear model based on significance scores between SNP （175A 〉 G） and heat stroke parameters. As a result, we found a significant association between SNP A175G and heat stroke （P ~ 0.05）. Further bioinformatics analysis of the 1-Mb flanking sequence revealed the presence of two genes that encode DDB1 and CUL4 associated factor 8 （DCAF8）, and peroxisomal biogenesis factor 19 （PEX19）, respectively, which might be functionally related to CASQ1. Our results showed that the blood calcium of patients with allele D increased significantly, compared to patients with allele N （P 〈 0.05）, which may result from the decreased calcium in muscle, suggesting that N59D in CASQ1 might account for the dysfunction of CASQ1 in calcium regulation during heat stroke.
基金the National Natural Sciences Foundation of China (No. 30672008)
文摘To investigate the distribution characteristics and linkage disequilibrium of T cell immunoglobulin domain and mucin domain protein 4 （TIM4） promoter polymorphisms in asthma patients of Chinese Han population, the promoter region of TIM4 was re-sequenced by PCR-sequencing, and linkage disequilibrium was analyzed by SHEsis software. Four single nucleotide polymor- phisms （SNPs） in the promoter region of TIM4 were detected, including two new SNPs （at positions -1609, -153） and two reported SNPs （rs6874202, rs6882076）. The frequency distribution of rs6882076 was different among different races （P〈0.05）. In addition, linkage disequilibrium among the SNPs of the promoter region of TIM4 was found and GGTG was the predominant haplotype. There were four SNPs in the promoter region of TIM4 in asthma patients of Chinese Han population, which were in linkage disequilibrium.
文摘Isothermal methods, such as helicase-dependent amplification （HDA）, have an advantage over polymerase chain reaction for DNA amplification owing to their ease of operation. Here, we developed a new HDA method that is nanoparticle-assisted, termed nanoHDA. This method uses gold nanoparticles （AuNPs） to improve the sensitivity and specificity of the isothermal method. In HDA, the denaturation of DNA templates is mediated by helicases, but this method is limited by the low denaturation efficiency of helicases. In this report, AuNPs with preferential affinity for single-stranded DNA （ssDNA） were utilized to improve the denaturation efficiency of helicases. The same affinity property of nanoparticles can also enhance specificity by suppressing primer-dimer formation. This nanoHDA method was employed to genotype the KRAS gene in genomic DNA samples from colorectal cancer patients, as achieved by the hybridization of nanoHDA amplicons using the NanoBioArray chip.
文摘AIM： To investigate the correlation between C/T single nucleotide polymorphism （SNP） in the promoter of the DNA methyltransferase 3B （D/VMT3B） gene and risk for development and progression of primary hepatocellular carcinoma （HCC）. METHODS： One hundred case subjects were selected consecutively from Tongji Hospital （Wuhan, China）. from March to November 2006. They did not receive radiotherapy or chemotherapy for newly diagnosed and histopathologically confirmed HCC. One hundred and forty control subjects having no history of cancerous or genetic diseases were healthy volunteers to Wuhan Blood Center in the same period. Frequency was matched for sex, age, alcohol consumption and cigarette smoking status of the case subjects. C/T polymorphism of the DNMT3B promoter was analyzed using polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） and sequencing analysis. The association between genotypes of DNMT3B and clinicopathological parameters among cases was also studied. RESULTS： The CC genotype HCC patients and controls. was not detected in both In control subjects, the frequency of TT and CT genotypes was 99.3% and 0.7% respectively, and that of T and C alleles was 99.6% and 0.4% respectively. The frequency of CT genotype was higher in HCC （3.0%）. The frequency of T and C alleles was 98.5% and 1.5% respectively. However, the genotype and allelotype distribution in HCC patients was not significantly different from that in controls. CONCLUSION： C/T polymorphism is not associated with the increased risk of HCC. DNMT3B genetic polymorphism is variable in different races, ethnic groups or geographic areas. Further study is needed to clarify the role of DNMT3B SNP in the development of HCCamong other populations.
文摘The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (SNPs) and determine the correlation of these changes with serum PSA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PSA determinations were done using ELISA technique while genetic studies were carried out using real-time PCR. tPSA, fPSA, and % fPSA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPSA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPSA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed SNPs with a mean tPSA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without SNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 SNPs. Ten subjects are curated in SNP database while one is uncurated. The Chi-square test showed significant association (p = 0.00) between tPSA levels and SNPs mutation (X<sup>2</sup> = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the SNP mutations had no effect on PSA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two SNPs: rs6072 and rs74478031 were associated with elevated PSA levels (p < 0.05). Their presence, therefore, has the potential to serve, in conjunction with raised PSA, as biomarkers of prostate cancer in the study population.
基金Supported by the National Natural Science Foundation of China, No. 30080016 and 30470977
文摘Neoplastic progression is generally characterized by the accumulation of multiple genetic alterations including loss of tumor suppression gene function. Loss of heterozygosity （LOH） has been used to identify genomic regions that harbor tumor suppressor genes and to characterize different tumor types, pathological stages and progression. LOH pattern has been detected by allelotyping using restriction fragment length polymorphism, and later by simple sequence length polymorphisms （SSLPs or microsatellite） for 10 years. This paper reviews the detection of LOH by recently developed single nucleotide polymorphism （SNP） arrays （all analyzed by Affymetrix array）; furthermore, its advantage and disadvantage were analyzed in several kinds of cancer.
基金the Fondazione Veronesi that granted Daniela Vivenza and Martino Monteverde with PostDoctoral Fellowship Veronesithe Fondazione Cassa Risparmio of Cuneo for partially supporting the study
文摘AIM:To investigate the prognostic role of invariant natural killer T(iNKT) cells and antibody-dependent cell-mediated cytotoxicity(ADCC) in wild type KRAS metastatic colorectal cancer(mC RC) patients treated with cetuximab.METHODS: Forty-one KRAS wt mC RC patients,treated with cetuximab and irinotecan-based chemotherapy in Ⅱ and Ⅲ lines were analyzed. Genotyping of single nucleotide polymorphism(SNP)s in the FCGR2A,FCGR3A and in the 3' untranslated regions of KRAS and mutational analysis for KRAS,BRAF and NRAS genes was determined either by sequencing or allelic discrimination assays. Enriched NK cells were obtained from lymphoprepperipheral blood mononuclear cell and iN KT cells were defined by co-expression of CD3,TCRVα24,TCRVβ11. ADCC was evaluated as ex vivo NK-dependent activity,measuring lactate dehydrogenase release.RESULTS: At basal,mCRC patients performing ADCC activity above the median level(71%) showed an improved overall survival(OS) compared to patients with ADCC below(median 16 vs 8 mo;P=0.026). We did not find any significant correlation of iN KT cells with OS(P=0.19),albeit we observed a trend to a longer survival after 10 mo in patients with iN KT above median basal level(0.382 cells/microliter). Correlation of OS and progression-free survival(PFS) with interesting SNPs involved in ADCC ability revealed not to be significant. Patients carrying alleles both with A in FCGR2 A and TT in FCGR3A presented a trend of longer PFS(median 9 vs 5 mo;P=0.064). Chemotherapy impacted both iN KT cells and ADCC activity. Their prognostic values get lost when we analysed them after 2 and 4 mo of treatment.CONCLUSION: Our results suggest a link between iN KT cells,basal ADCC activity,genotypes in FCGR2A and FCGR3A,and efficacy of cetuximab in KRAS wt mC RC patients.
文摘Here, we report a method that uses gold nanoparticles （AuNPs） to enhance the specificity of DNA hybridization without reducing its detection sensitivity. The conventional stringent wash method utilizes high-temperatureflow-salt conditions to enhance the specificity of DNA hybridization-based assays. This method creates a destabilizing environment for base pairing that affects specific and nonspecific duplexes. Therefore, specificity is achieved at the expense of signal intensity or sensitivity. However, in the proposed wash method, AuNPs predominantly destabilize nonspecific duplexes, offering specificity without compromising sensitivity. This AuNP wash technique has proven to be effective in detecting single nucleotide polymorphisms （SNPs） in genomic samples even at room temperature in a CD-like NanoBioArray （CD-NBA） chip. This method is also robust with sequence variation and is compatible with multiplex DNA analyses on microarrays. Thus, the AuNP wash method could potentially be useful for improving the accuracy of DNA hybridization results.
基金Supported by National Natural Science Foundation of China,No.81471670 and No.81102711the International Cooperative Project of Shaanxi Province,China,No.2013KW-32-01the Fundamental Research Funds for the Central Universities,China and Specialized Research Fund of the Second Affiliated Hospital of Xi'an Jiaotong University,China,No.RC(GG)201203
文摘AIM:To evaluate the relationship between apurinic endonuclease 1(APE1) Asp148 Glu polymorphism and the susceptibility to gastrointestinal(GI) cancers.METHODS:We searched Pub Med, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure(CNKI) databases updated on July 15, 2014 for relevant studies.Only case-control studies comparing APE1 Asp148 Glu polymorphism and GI cancer risk were included.We excluded studies reporting only standardized incidence ratios without control groups and those without detailed genotyping data.Meta-analysis was performed on 17 studies involving 4856 cancer patients and 6136 cancer-free controls.Review Manager version 5.1 was used to perform the meta-analysis.The pooled odds ratios(ORs) and 95% confidence intervals(CIs) were estimated under the allele contrast, homozygous, heterozygous, dominant and recessive genetic models.We also conducted subgroup analyses stratified by ethnicity and cancer type.Publication bias was evaluated using Begg's test.RESULTS:The meta-analysis showed a significant association between APE1 Asp148Glu polymorphism and GI cancer risk in three genetic models in the overall population(G vs T:OR=1.18;95%CI:1.05-1.32;TG vs TT:OR=1.28;95%CI:1.08-1.52;TG+GG vs TT:OR=1.32;95%CI:1.10-1.57).Stratified analysis by ethnicity revealed a statistically increased GI cancer risk in Asians(G vs T:OR=1.27;95%CI:1.07-1.51;GG vs TT:OR=1.58;95%CI:1.05-2.38;TG vs TT:OR=1.30;95%CI,1.01-1.67;and TG+GG vs TT:OR=1.38;95%CI:1.07-1.78),but not in Caucasians.Furthersubgroup analysis by cancer type indicated that APE1Asp148Glu polymorphism may contribute to gastric cancer risk.However,Asp148Glu has no significant association with colorectal or esophageal cancer risk in any genetic model.CONCLUSION:This meta-analysis suggests that the APE1 Asp148Glu polymorphism G allele is associated with an increased GI cancer risk,especially in gastric cancer.
