FOXO1Gene Polymorphisms, Environment Factors And Gene-Environment Interactions In The Development Of Type2Diabetes Mellitus

Type2diabetes mellitus (T2DM) is a complex polygenic disease, accounting formore than90%of diabetes mellitus. In recent years, the prevalence of diabetes hasbeen rising constantly, with371million people having diabetes in2012. By2030thisfigure would have risen to552million. The pathogenesis of T2DM is very complex,mainly associated with insulin resistance and pancreatic beta cell function defects.Evidence has more recently emerged that forkhead box protein O1(FOXO1) playsimportant roles in a variety of biological functions, such as regulation ofgluconeogenesis, β cell function, fat cell differentiation and lipid metabolism,,which may be associated with T2DM.Objective To investigate the association between FOXO1gene polymorphismand T2DM; screen out T2DM environmental risk factors; and explore thegene-environment interactions in the development of T2DM.Methods Using case-control study design,395cases of T2DM patients wererecruited in the case group and372healthy persons were selected as control group.The method of Matrix-Assisted Laser Desorption/Ionization Time of Flight MassSpectrometry (MALI-TOF-MS) was applied to detect the SNPs (rs2755213,rs2701880, rs10507486) of FOXO1gene. The database was established byEpdidata3.1software. Using SPSS16.0statistical software, Haploview4.2UNPHASED3.1.4software to perform statistical analysis. Mean±standard deviationwas used when continuous data was normally-distributed, t-test was used to test the differences of continuous data between case and control; rate and ratio was used todescribe categorical data, using χ2test to test the differences of categorical data. Thegoodness of fit χ2test was used to test Hardy-Weinberg equilibrium in the cases andcontrols. Using χ2test to test the differences of genotype and allele frequenciesbetween case and control. χ2test was used for univariate analyses of T2DMenvironmental factors.Using multivariable non-conditional logistic regression modelto test multivariate analysis and gene-environment interaction analysis.Results①The study recruited385T2DM patients as case group and372healthy person as control group, the differences in age and gender distributionbetween the two groups has no statistically significant.②The genotype frequenciesdistribution of rs2755213, rs2701880, rs10507486between case and control groupswere accorded with Hardy-Weinberg equilibrium law (P>0.05).③There were nosignificant differences in the frequencies of the alleles and the genotypes atrs2755213,rs2701880sites between the two groups (P>0.05); the differences ingenotype and allele frequencies distribution at rs10507486between two groups weresignificant(P<0.05), T mutation of rs10507486site was a risk factor ofT2DM(OR=1.42，95%CI=1.03~1.97).④There were no significant differences in thedistribution of haplotypes formatted by rs2755213, rs2701880, rs10507486sitebetween the two groups (P>0.05).⑤The results of univariate analysis showed thatfamily history of diabetes, WHR(male≥0.90, female≥0.85), BMI≥24Kg/m~2, TC≥6.62mmol/L, TG≥2.26mmol/L, HDL-C<1.04mmol/L were risk factors forT2DM(P<0.05); alcohol intake, always eating fruits and always drinking milk andmilk products were protective factors for T2DM(P<0.05).⑥The results ofmultivariate analysis showed that BMI≥24Kg/m~2, TG≥.26mmol/L, HDL-C＜1.04mmol/L were risk factors of T2DM(P＜0.05).⑦The interaction analysis indicatedthat there was a negative plus interaction between rs2755213polymorphisms and TG.Conclusion①There was a certain correlation between rs10507486polymorphism and T2DM, and rs10507486site mutated from C to T was a risk factorof T2DM.②rs2755213and rs2701880polymorphisms were not associated with T2DM.③There were no association between the haplotypes formatted by rs2755213,rs2701880, rs10507486site and T2DM.④BMI≥24Kg/m~2, TG≥2.26mmol/L,HDL-C＜1.04mmol/L were risk factors of T2DM.