In anther development, tapetal cells take part in complex processes, including endomitosis and apoptosis （programmed cell death）. The tapetum provides many of the proteins, lipids, polysaccharides and other molecule...In anther development, tapetal cells take part in complex processes, including endomitosis and apoptosis （programmed cell death）. The tapetum provides many of the proteins, lipids, polysaccharides and other molecules necessary for pollen development. Several transcription factors, including DYT1, TDF1, AMS, MS188 and MS1, have been reported to be essential for tapetum development and function in Arabidopsis thaliana. Here, we present a detailed cytological analysis of knockout mutants for these genes, along with an in situ RNA hybridization experiment and double mutant analysis showing that these transcription factors form a genetic pathway in tapetum development. DYT1, TDF1 and AMS function in early tapetum development, while MS188 and MS1 are important for late tapetum development. The genetic pathway revealed in this work facilitates further investigation of the function and molecular mechanisms of tapetum development in Arabidopsis.展开更多
开花时间对植物的繁殖成功至关重要。广泛分布的物种经常发生开花时间的分化,从而能够更好地适应不同的环境条件。为了探索植物开花行为发生适应性分化的分子机制,首先要明确调控开花行为的遗传通路。本文梳理了植物各类群调控开花时间...开花时间对植物的繁殖成功至关重要。广泛分布的物种经常发生开花时间的分化,从而能够更好地适应不同的环境条件。为了探索植物开花行为发生适应性分化的分子机制,首先要明确调控开花行为的遗传通路。本文梳理了植物各类群调控开花时间的遗传通路,以期为开花时间适应性分化的分子机制研究提供依据。植物从营养生长向繁殖转变时,其开花行为主要受到光照、温度、水分等外界环境因子和赤霉素等内在因素的影响。通过对模式植物拟南芥(Arabidopsis thaliana)和其他类群的研究,总结出了调控植物开花时间的6条通路,包括日照长度和光质影响开花的光依赖通路,长时间冷暴露后促进植物开花的春化通路,高温或低温环境影响开花的温度通路,以及赤霉素通路、年龄通路和自主通路3条内部调节过程。植物开花时间调控的6条上游通路信号传递到下游的开花整合基因FT(FLOWERING LOCUS T)和SOC1(SUPPRESSOR OF OVER-EXPRESSION OF CONSTANS 1),整合基因将这些复杂的调节因子整合后进一步传递到下游花分生组织,从而启动开花。此外,非编码RNA、转座子对开花时间的调控也具有重要作用。部分遗传通路被证实在植物适应环境的过程中起到了重要作用。目前对植物开花调控的研究已经有一百多年历史,理论相对成熟。然而,仍然存在许多具有争议和未解决的问题,如开花基因的表达方式、开花行为的特殊调控机制、开花时间变异的适应性意义等等,需要更进一步的研究。展开更多
Colorectal cancer(CRC)results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma.Approximately 75%of CRCs are sporadic an...Colorectal cancer(CRC)results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma.Approximately 75%of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC.During the past two decades,sporadic CRCs were classified into three major groups according to frequently altered/mutated genes.These genes have been identified by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data.In the first half of this review,we describe the genetic pathways of sporadic CRCs and their clinicopathologic features.Recently,large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes.These infrequently mutated genes are likely described in a limited number of pathways.Gene-oriented models of CRC progression are being replaced by pathway-oriented models.In the second half of this review,we summarize the present knowledge of this research field and discuss its prospects.展开更多
Metabolic syndrome(MetS)is a clustering of metabolic abnormalities that is associated with increased risk of developing cardiovascular disease and type 2 diabetes.There is growing body of data showing the associations...Metabolic syndrome(MetS)is a clustering of metabolic abnormalities that is associated with increased risk of developing cardiovascular disease and type 2 diabetes.There is growing body of data showing the associations of genetic variants of the genes involved in the PI3K/AKT/mTOR pathway with diabetes and obesity.We aimed to investigate the association between MetS and its components with the genetic polymorphism in AKT1,rs1130233(T>C).Total of 618 participants,recruited from Mashhad stroke and heart atherosclerosis disorder cohort(MASHAD study).Patients with MetS were defined by using international diabetes federation(IDF)criteria(n Z 326)and those without MetS(n Z 261)were recruited.Anthropometric and biochemical parameters were measured in all subjects.Genetic analysis for the rs1130233 polymorphism was performed,using the ABI-StepOne instruments with SDS version-2.0 software.Individuals with MetS had a significantly higher levels of BMI,waistcircumference,total cholesterol,triglyceride,high sensitivity-c reactive protein(hs-CRP)and blood-pressure,and lower concentrations of high density lipoprotein(HDL-C),compared to non-MetS individuals(P<0.05).The association between the rs1130233 and MetS was not significant.Subjects with a CC or CT genotypes had a significantly higher serum hs-CRP-level(OR:1.5;95%CI(1.05e2.1),P Z 0.02).Additionally,subjects who carried the TC genotype had a higher BMI compared to the CC genotype(p value Z 0.045).Our findings demonstrated that AKT1,rs1130233(T>C)polymorphism was associated with major components of MetS such as hs-CRP,and BMI,indicating further investigation in a multi-center setting to explore its value as an emerging biomarker of risk stratification marker.展开更多
Coronary artery disease （CAD） is a complex human disease, involving multiple genes and their nonlinear interactions, which often act in a modular fashion. Genome-wide single nucleotide polymorphism （SNP） profiling...Coronary artery disease （CAD） is a complex human disease, involving multiple genes and their nonlinear interactions, which often act in a modular fashion. Genome-wide single nucleotide polymorphism （SNP） profiling provides an effective technique to unravel these underlying genetic interplays or their functional involvements for CAD. This study aimed to identify the susceptible pathways and modules for CAD based on SNP omics. First, the Wellcome Trust Case Control Consortium （WTCCC） SNP datasets of CAD and control samples were used to assess the joint effect of multiple genetic variants at the pathway level, using logistic kernel machine regression model. Then, an expanded genetic network was constructed by integrating statistical gene-gene interactions involved in these susceptible pathways with their protein protein interaction （PPI） knowledge. Finally, risk functional modules were identified by decomposition of the network. Of 276 KEGG pathways analyzed, 6 pathways were found to have a significant effect on CAD. Other than glycerolipid metabolism, glycosaminoglycan biosynthesis, and cardiac muscle contraction pathways, three pathways related to other diseases were also revealed, including Alzheimer＇s disease, non-alcoholic fatty liver disease, and Huntington＇s disease. A genetic epistatic network of 95 genes was further constructed using the abovementioned integrative approach. Of 10 functional modules derived from the network, 6 have been annotated to phospholipase C activity and cell adhesion molecule binding, which also have known functional involvement in Alzheimer＇s disease. These findings indicate an overlap of the underlying molecular mechanisms between CAD and Alzheimer＇s disease, thus providing new insights into the molecular basis for CAD and its molecular relationships with other diseases.展开更多
Abstract: Over the past decade, the evolving commercial importance of so-called plant secondary metabolites has resulted in a great interest in secondary metabolism and, particularly, in the possibilities to enhance t...Abstract: Over the past decade, the evolving commercial importance of so-called plant secondary metabolites has resulted in a great interest in secondary metabolism and, particularly, in the possibilities to enhance the yield of fine metabolites by means of genetic engineering. Plant alkaloids, which constitute one of the largest groups of natural products, provide many pharmacologically active compounds. Several genes in the tropane alkaloids biosynthesis pathways have been cloned, making the metabolic engineering of these alkaloids possible. The content of the target chemical scopolamine could be significantly increased by various approaches, such as introducing genes encoding the key biosynthetic enzymes or genes encoding regulatory proteins to overcome the specific rate-limiting steps. In addition, antisense genes have been used to block competitive pathways. These investigations have opened up new, promising perspectives for increased production in plants or plant cell culture. Recent achievements have been made in the metabolic engineering of plant tropane alkaloids and some new powerful strategies are reviewed in the present paper.展开更多
Signal transduction plays important roles in biological systems. Unfortunately, our knowledge about signaling pathways is far from complete. Specifically, the direction of signaling flows is less known even though the...Signal transduction plays important roles in biological systems. Unfortunately, our knowledge about signaling pathways is far from complete. Specifically, the direction of signaling flows is less known even though the signaling molecules of some signaling pathways have been determined. In this paper, we propose a novel hybrid intelligent method, namely HISP （Hybrid Intelligent approach for identifying directed Signaling Pathways）, to determine both the topologies of signaling pathways and the direction of signaling flows within a pathway based on integer linear programming and genetic algorithm. By integrating the protein-protein interaction, gene expression, and gene knockout data, our HISP approach is able to determine the optimal topologies of signaling pathways in an accurate way. Benchmark results on yeast MAPK signaling pathways demonstrate the efficiency of our proposed approach. When applied to the EGFR/ErbB signaling pathway in human hepatocytes, HISP unveils a high-resolution signaling path- way, where many signaling interactions were missing by existing computational approaches.展开更多
AIM: To investigate the associations between the polymorphisms of cell cycle pathway genes and the risk of hepatocellular carcinoma(HCC). METHODS: We enrolled 1127 cases newly diagnosed with HCC from the Tumor Hospita...AIM: To investigate the associations between the polymorphisms of cell cycle pathway genes and the risk of hepatocellular carcinoma(HCC). METHODS: We enrolled 1127 cases newly diagnosed with HCC from the Tumor Hospital of Guangxi Medical University and 1200 non-tumor patients from the First Affiliated Hospital of Guangxi Medical University. General demographic characteristics, behavioral information, and hematological indices were collected by unified questionnaires. Genomic DNA was isolatedfrom peripheral venous blood using Phenol-Chloroform. The genotyping was performed using the Sequenom Mass ARRAY i PLEX genotyping method. The association between genetic polymorphisms and risk of HCC was shown by P-value and the odd ratio(OR) with 95% confidence interval(CI) using the unconditional logistic regression after adjusting for age, sex, nationality, smoking, drinking, family history of HCC, and hepatitis B virus(HBV) infection. Moreover, stratified analysis was conducted on the basis of the status of HBV infection, smoking, and alcohol drinking.RESULTS: The HCC risk was lower in patients with the MCM4 rs2305952 CC(OR = 0.22, 95%CI: 0.08-0.63, P = 0.01) and with the CHEK1 rs515255 TC, TT, TC/TT(OR = 0.73, 95%CI: 0.56-0.96, P = 0.02; OR = 0.67, 95%CI: 0.46-0.97, P = 0.04; OR = 0.72, 95%CI: 0.56-0.92, P = 0.01, respectively). Conversely, the HCC risk was higher in patients with the KAT2 B rs17006625 GG(OR = 1.64, 95%CI: 1.01-2.64, P = 0.04). In addition, the risk was markedly lower for those who were carriers of MCM4 rs2305952 CC and were also HBs Ag-positive and non-drinking and nonsmoking(P < 0.05, respectively) and for those who were carriers of CHEK1 rs515255 TC, TT, TC/TT and were also HBs Ag-negative and non-drinking(P < 0.05, respectively). Moreover, the risk was higher for those who were carriers of KAT2 B rs17006625 GG and were also HBs Ag-negative(P < 0.05).CONCLUSION: Of 12 cell cycle pathway genes, MCM4, CHEK1 and KAT2 B polymorphisms may be associated with the risk of HCC.展开更多
AIM: To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms (SNPs) and gastric cancer risk in Venezuelan patients.METHODS: We performed a case-control study including 122 pa...AIM: To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms (SNPs) and gastric cancer risk in Venezuelan patients.METHODS: We performed a case-control study including 122 paraffin-embedded archived intestinal-type gastric cancer samples and 129 biopsies obtained by superior endoscopy from chronic gastritis patients. Gastric cancer samples were classified according the degree of carcinoma differentiation. Genomic DNA was extracted from tissues, and the two SNPs of TCF7L2 gene (rs12255372 and rs7903146) were genotyped by polymerase chain reaction-restriction fragment length polymorphism reactions. Multiple regression analysis with adjustments for age and gender were performed and best-fitting models of inheritance were determined. Statistic powers were post-hoc calculated.RESULTS: After adjusting for age and sex the TCF7L2 rs7903146 TT genotype was associated with gastric cancer risk under the recessive genetic model (OR = 3.11, 95%CI: 1.22-7.92, P = 0.017). We further investigated the distribution of rs12255372 and rs7903146 genotypes according gastric cancer stratified by degree of differentiation, and we observed that carriers of rs7903146 T allele (CT + TT vs CC) had a significantly increased risk of moderate/well differentiated gastric cancer (dominant model, OR = 2.55, 95%CI: 1.35-4.80, P = 0.004), whereas the rs7903146 TT genotype was associated with poorly differentiated gastric cancer in the recessive model (OR = 3.65, 95%CI: 1.25-10.62, P = 0.018). We did not find association between rs12255372 SNP and the susceptibility of developing gastric cancer.CONCLUSION: TCF7L2 rs7903146 polymorphism is associated with gastric cancer risk in the Venezuelan population, and could be related to determine the degree of differentiation of tumor cells.展开更多
基金supported by grants from the National Natural Science Foundation of China (30925007)Shanghai(11ZR1425800)the State Key Basic Research and Development Program of China (2007CB947600)
文摘In anther development, tapetal cells take part in complex processes, including endomitosis and apoptosis （programmed cell death）. The tapetum provides many of the proteins, lipids, polysaccharides and other molecules necessary for pollen development. Several transcription factors, including DYT1, TDF1, AMS, MS188 and MS1, have been reported to be essential for tapetum development and function in Arabidopsis thaliana. Here, we present a detailed cytological analysis of knockout mutants for these genes, along with an in situ RNA hybridization experiment and double mutant analysis showing that these transcription factors form a genetic pathway in tapetum development. DYT1, TDF1 and AMS function in early tapetum development, while MS188 and MS1 are important for late tapetum development. The genetic pathway revealed in this work facilitates further investigation of the function and molecular mechanisms of tapetum development in Arabidopsis.
文摘开花时间对植物的繁殖成功至关重要。广泛分布的物种经常发生开花时间的分化,从而能够更好地适应不同的环境条件。为了探索植物开花行为发生适应性分化的分子机制,首先要明确调控开花行为的遗传通路。本文梳理了植物各类群调控开花时间的遗传通路,以期为开花时间适应性分化的分子机制研究提供依据。植物从营养生长向繁殖转变时,其开花行为主要受到光照、温度、水分等外界环境因子和赤霉素等内在因素的影响。通过对模式植物拟南芥(Arabidopsis thaliana)和其他类群的研究,总结出了调控植物开花时间的6条通路,包括日照长度和光质影响开花的光依赖通路,长时间冷暴露后促进植物开花的春化通路,高温或低温环境影响开花的温度通路,以及赤霉素通路、年龄通路和自主通路3条内部调节过程。植物开花时间调控的6条上游通路信号传递到下游的开花整合基因FT(FLOWERING LOCUS T)和SOC1(SUPPRESSOR OF OVER-EXPRESSION OF CONSTANS 1),整合基因将这些复杂的调节因子整合后进一步传递到下游花分生组织,从而启动开花。此外,非编码RNA、转座子对开花时间的调控也具有重要作用。部分遗传通路被证实在植物适应环境的过程中起到了重要作用。目前对植物开花调控的研究已经有一百多年历史,理论相对成熟。然而,仍然存在许多具有争议和未解决的问题,如开花基因的表达方式、开花行为的特殊调控机制、开花时间变异的适应性意义等等,需要更进一步的研究。
文摘Colorectal cancer(CRC)results from the progressive accumulation of genetic and epigenetic alterations that lead to the transformation of normal colonic mucosa to adenocarcinoma.Approximately 75%of CRCs are sporadic and occur in people without genetic predisposition or family history of CRC.During the past two decades,sporadic CRCs were classified into three major groups according to frequently altered/mutated genes.These genes have been identified by linkage analyses of cancer-prone families and by individual mutation analyses of candidate genes selected on the basis of functional data.In the first half of this review,we describe the genetic pathways of sporadic CRCs and their clinicopathologic features.Recently,large-scale genome analyses have detected many infrequently mutated genes as well as a small number of frequently mutated genes.These infrequently mutated genes are likely described in a limited number of pathways.Gene-oriented models of CRC progression are being replaced by pathway-oriented models.In the second half of this review,we summarize the present knowledge of this research field and discuss its prospects.
基金We would like to thank Research Council of Mashhad University of Medical Science and Hakim Sabzevary University for their financial supports.
文摘Metabolic syndrome(MetS)is a clustering of metabolic abnormalities that is associated with increased risk of developing cardiovascular disease and type 2 diabetes.There is growing body of data showing the associations of genetic variants of the genes involved in the PI3K/AKT/mTOR pathway with diabetes and obesity.We aimed to investigate the association between MetS and its components with the genetic polymorphism in AKT1,rs1130233(T>C).Total of 618 participants,recruited from Mashhad stroke and heart atherosclerosis disorder cohort(MASHAD study).Patients with MetS were defined by using international diabetes federation(IDF)criteria(n Z 326)and those without MetS(n Z 261)were recruited.Anthropometric and biochemical parameters were measured in all subjects.Genetic analysis for the rs1130233 polymorphism was performed,using the ABI-StepOne instruments with SDS version-2.0 software.Individuals with MetS had a significantly higher levels of BMI,waistcircumference,total cholesterol,triglyceride,high sensitivity-c reactive protein(hs-CRP)and blood-pressure,and lower concentrations of high density lipoprotein(HDL-C),compared to non-MetS individuals(P<0.05).The association between the rs1130233 and MetS was not significant.Subjects with a CC or CT genotypes had a significantly higher serum hs-CRP-level(OR:1.5;95%CI(1.05e2.1),P Z 0.02).Additionally,subjects who carried the TC genotype had a higher BMI compared to the CC genotype(p value Z 0.045).Our findings demonstrated that AKT1,rs1130233(T>C)polymorphism was associated with major components of MetS such as hs-CRP,and BMI,indicating further investigation in a multi-center setting to explore its value as an emerging biomarker of risk stratification marker.
基金supported in part by the National Natural Science Foundation of China(Grant Nos.31071166 and 81373085)Natural Science Foundation of Guangdong Province,China(Grant No.8251008901000007)+2 种基金Science and Technology Planning Project of Guangdong Province(Grant No.2009A030301004)Dongguan Science and Technology Project,Guangdong,China(Grant No.2011108101015)the funds from Guangdong Medical College,China(Grant Nos.XG1001,JB1214,XZ1105,STIF201122,M2011024,and M2011010)
文摘Coronary artery disease （CAD） is a complex human disease, involving multiple genes and their nonlinear interactions, which often act in a modular fashion. Genome-wide single nucleotide polymorphism （SNP） profiling provides an effective technique to unravel these underlying genetic interplays or their functional involvements for CAD. This study aimed to identify the susceptible pathways and modules for CAD based on SNP omics. First, the Wellcome Trust Case Control Consortium （WTCCC） SNP datasets of CAD and control samples were used to assess the joint effect of multiple genetic variants at the pathway level, using logistic kernel machine regression model. Then, an expanded genetic network was constructed by integrating statistical gene-gene interactions involved in these susceptible pathways with their protein protein interaction （PPI） knowledge. Finally, risk functional modules were identified by decomposition of the network. Of 276 KEGG pathways analyzed, 6 pathways were found to have a significant effect on CAD. Other than glycerolipid metabolism, glycosaminoglycan biosynthesis, and cardiac muscle contraction pathways, three pathways related to other diseases were also revealed, including Alzheimer＇s disease, non-alcoholic fatty liver disease, and Huntington＇s disease. A genetic epistatic network of 95 genes was further constructed using the abovementioned integrative approach. Of 10 functional modules derived from the network, 6 have been annotated to phospholipase C activity and cell adhesion molecule binding, which also have known functional involvement in Alzheimer＇s disease. These findings indicate an overlap of the underlying molecular mechanisms between CAD and Alzheimer＇s disease, thus providing new insights into the molecular basis for CAD and its molecular relationships with other diseases.
文摘Abstract: Over the past decade, the evolving commercial importance of so-called plant secondary metabolites has resulted in a great interest in secondary metabolism and, particularly, in the possibilities to enhance the yield of fine metabolites by means of genetic engineering. Plant alkaloids, which constitute one of the largest groups of natural products, provide many pharmacologically active compounds. Several genes in the tropane alkaloids biosynthesis pathways have been cloned, making the metabolic engineering of these alkaloids possible. The content of the target chemical scopolamine could be significantly increased by various approaches, such as introducing genes encoding the key biosynthetic enzymes or genes encoding regulatory proteins to overcome the specific rate-limiting steps. In addition, antisense genes have been used to block competitive pathways. These investigations have opened up new, promising perspectives for increased production in plants or plant cell culture. Recent achievements have been made in the metabolic engineering of plant tropane alkaloids and some new powerful strategies are reviewed in the present paper.
文摘Signal transduction plays important roles in biological systems. Unfortunately, our knowledge about signaling pathways is far from complete. Specifically, the direction of signaling flows is less known even though the signaling molecules of some signaling pathways have been determined. In this paper, we propose a novel hybrid intelligent method, namely HISP （Hybrid Intelligent approach for identifying directed Signaling Pathways）, to determine both the topologies of signaling pathways and the direction of signaling flows within a pathway based on integer linear programming and genetic algorithm. By integrating the protein-protein interaction, gene expression, and gene knockout data, our HISP approach is able to determine the optimal topologies of signaling pathways in an accurate way. Benchmark results on yeast MAPK signaling pathways demonstrate the efficiency of our proposed approach. When applied to the EGFR/ErbB signaling pathway in human hepatocytes, HISP unveils a high-resolution signaling path- way, where many signaling interactions were missing by existing computational approaches.
基金Supported by National Natural Science Foundation of China,No.81360448Natural Science Foundation of Guangxi,No.2014GXNSFAA118139+1 种基金Fund of Key Laboratory of High Incidence-Tumor Prevention and Treatment(Guangxi Medical University),Ministry of Education,No.GK2015-ZZ03 and No.GK2014-ZZ03Guangxi Outstanding Teacher Training Project for Colleges
文摘AIM: To investigate the associations between the polymorphisms of cell cycle pathway genes and the risk of hepatocellular carcinoma(HCC). METHODS: We enrolled 1127 cases newly diagnosed with HCC from the Tumor Hospital of Guangxi Medical University and 1200 non-tumor patients from the First Affiliated Hospital of Guangxi Medical University. General demographic characteristics, behavioral information, and hematological indices were collected by unified questionnaires. Genomic DNA was isolatedfrom peripheral venous blood using Phenol-Chloroform. The genotyping was performed using the Sequenom Mass ARRAY i PLEX genotyping method. The association between genetic polymorphisms and risk of HCC was shown by P-value and the odd ratio(OR) with 95% confidence interval(CI) using the unconditional logistic regression after adjusting for age, sex, nationality, smoking, drinking, family history of HCC, and hepatitis B virus(HBV) infection. Moreover, stratified analysis was conducted on the basis of the status of HBV infection, smoking, and alcohol drinking.RESULTS: The HCC risk was lower in patients with the MCM4 rs2305952 CC(OR = 0.22, 95%CI: 0.08-0.63, P = 0.01) and with the CHEK1 rs515255 TC, TT, TC/TT(OR = 0.73, 95%CI: 0.56-0.96, P = 0.02; OR = 0.67, 95%CI: 0.46-0.97, P = 0.04; OR = 0.72, 95%CI: 0.56-0.92, P = 0.01, respectively). Conversely, the HCC risk was higher in patients with the KAT2 B rs17006625 GG(OR = 1.64, 95%CI: 1.01-2.64, P = 0.04). In addition, the risk was markedly lower for those who were carriers of MCM4 rs2305952 CC and were also HBs Ag-positive and non-drinking and nonsmoking(P < 0.05, respectively) and for those who were carriers of CHEK1 rs515255 TC, TT, TC/TT and were also HBs Ag-negative and non-drinking(P < 0.05, respectively). Moreover, the risk was higher for those who were carriers of KAT2 B rs17006625 GG and were also HBs Ag-negative(P < 0.05).CONCLUSION: Of 12 cell cycle pathway genes, MCM4, CHEK1 and KAT2 B polymorphisms may be associated with the risk of HCC.
文摘AIM: To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms (SNPs) and gastric cancer risk in Venezuelan patients.METHODS: We performed a case-control study including 122 paraffin-embedded archived intestinal-type gastric cancer samples and 129 biopsies obtained by superior endoscopy from chronic gastritis patients. Gastric cancer samples were classified according the degree of carcinoma differentiation. Genomic DNA was extracted from tissues, and the two SNPs of TCF7L2 gene (rs12255372 and rs7903146) were genotyped by polymerase chain reaction-restriction fragment length polymorphism reactions. Multiple regression analysis with adjustments for age and gender were performed and best-fitting models of inheritance were determined. Statistic powers were post-hoc calculated.RESULTS: After adjusting for age and sex the TCF7L2 rs7903146 TT genotype was associated with gastric cancer risk under the recessive genetic model (OR = 3.11, 95%CI: 1.22-7.92, P = 0.017). We further investigated the distribution of rs12255372 and rs7903146 genotypes according gastric cancer stratified by degree of differentiation, and we observed that carriers of rs7903146 T allele (CT + TT vs CC) had a significantly increased risk of moderate/well differentiated gastric cancer (dominant model, OR = 2.55, 95%CI: 1.35-4.80, P = 0.004), whereas the rs7903146 TT genotype was associated with poorly differentiated gastric cancer in the recessive model (OR = 3.65, 95%CI: 1.25-10.62, P = 0.018). We did not find association between rs12255372 SNP and the susceptibility of developing gastric cancer.CONCLUSION: TCF7L2 rs7903146 polymorphism is associated with gastric cancer risk in the Venezuelan population, and could be related to determine the degree of differentiation of tumor cells.
