Association Of NCOR2and FOXA1, Co-regulators Of ERα, Gene Polymorphisms With Type2Diabetes Mellitus

Type2diabetes mellitus (T2DM)is a multifactorial endocrine disease which isinduced by the interaction between multiple genes and numerous environmentalfactors.In recent years, the prevalence of diabetes has been rising constantly.However,the pathogenesis of diabetes remains largely unknown. A large number of candidategenes involved in the etiology of T2DM have been unraveled as a result of thedevelopment of molecular biology technology. The nuclear receptor corepressor2(NCOR2) gene and the forkhead box A1(FOXA1) geneare all co-regulators ofestrogen receptor α (ERα) and couldregulatethe activity of ERα. Many studies haveproved the important association between ERαand glycometabolism. So there may beassociation between NOCR2gene, FOXA1gene and T2DM.Objective To evaluate the association of single nucleotide polymorphisms(SNPs) in the NCOR2gene and FOXA1gene with T2DM; screen out theenvironmental risk factorsof T2DM; and explore the gene-gene interactions andgene-environment interactions in the development of T2DM.Methods Acase-control design was used to collect the information of395T2DM patients and372controls. The SNPs of NOCR2gene (rs1263992、rs1702339、rs747443、rs864503、rs12821657) and FOXA1gene (rs7144658) were genotyped byMatrix-Assited Laser Desorption/Ionization Time of Flight MassSpectromety(MALI-TOF-MS).The database was established by Epidata3.02software.Data analysis was done with SPSS16.0for Windows, Haploview4.2software, and online SNPStats program.For continuous data accord with normaldistribution, t test was used to compare between groups; for categorical data, χ2testwas used to comparethe rate and ratiobetween case and control. Association betweenSNPs, other variables and type2diabetes was also confirmed by χ2test. The Hardy-Weinberg equilibriumwas test using the goodness of fit χ2test. The interactionwas analyzed using multivariable non-conditional logistic regression model.Results①A total number of798subjects including395cases with T2DMand372controls were recruited. There was no significant difference between case andcontrol in age and gender (P＞0.05).②The SNPs of rs1263992, rs1702339,rs747443, rs864503, rs12821657and rs7144658in control were consistent withHardy-Weinberg equilibrium(P＞0.05).③There was no significant difference ofallele or genotype frequencies in all the loci between case and control (P＞0.05).④There was no significant differencein the genetic models between case and control (P＞0.05).⑤The haplotype A-G-C-T-T in NOCR2was significantly associated withT2DM (P＜0.05).⑥The results of univariate analysis showed that non-physicallabor, family history of diabetes, abnormal BMI, abnormal WHR, dyslipidemia,physical exercise, and no weight control were risk factors of T2DM; drinking, eatingfruit and aquatic product usually were protect factors of T2DM (P＜0.05).⑦Theresults of multivariate analysis showed that the family history of diabetes, abnormalBMI, TG≥2.26mmol/L were risk factors of T2DM; eating fruits usually were protectfactors of T2DM (P＜0.05).⑧No interaction was found between FOXA1rs7144658and NCOR2rs1263992, rs1702339, rs747443, rs864503, rs12821657(P＞0.05).⑨There was interaction between rs747443and BMI for T2DM (P＜0.05).Conclusion①No significant association was found between the SNPs ofNOCR2geneand T2DM.②There was association between the haplotypeA-G-C-T-Tand T2DM.③Family history of diabetes, obesity, dyslipidemia, lack ofphysical activity were risk factors of T2DM; eating fruit and aquatic product usuallywere protect factors of T2DM.④There was interaction between rs747443and BMIfor T2DM.