Association Of EIF2S1 And MAPK1 Gene Polymorphism With The Risk Of Type 2 Diabetes

Objective: The aim of this study was to explore the association of the rs6573769 polymorphism on the EIF2S1 gene,the rs3810610 and rs13515 polymorphisms on the MAPK1 gene and the risk of type 2 diabetes(T2DM)and its related physiological and biochemical indicators in the Han population of Guangxi.Finding risk SNPs that may be associated with T2 DM disease,and exploring the effects of the interaction between EIF2S1 and MAPK1 genes,gene and environmental factors on T2 DM.Providing a scientific reference for early screening and prevention of T2 DM susceptible population.Methods: A 1:1 matched case-control study was conducted to select populations from multiple communities in Nanning,Guangxi,and matched by gender and age(±5 years).A total of 843 pairs of case and controls were selected.The EIF2S1 gene rs6573769,MAPK1 gene rs3810610 and rs13515 were genotyped using the Mass ARRAY flight mass spectrometry system.The database was established by Epidata 3.1 software.The comparison of qualitative data between groups was performed by using Bowker test;The mean difference between the two groups was compared by using the paired-samples t test;The covariance analysis the association between the polymorphisms of each SNPs and the physiological and biochemical indicators after adjusting the relevant confounding factors;The above statistical analysis were performed by SPSS 19.0 software.The PLINK 1.07 software was used to analyze the Hardy-Weinberg genetic equilibrium test in the control group,and the difference of the genotype and allele frequency in each SNPs between the case and the control group,and the association between the SNPs and T2 DM.The SHEsis online platform performs linkage disequilibrium and haplotype analysis of SNPs on the same chromosome.The interaction model between two genes,MAPK1 gene and EIF2S1 gene and environment was constructed by generalized multi-factor dimensionality reduction method using GMDR 0.9 software.Results:(1)In this study,we selected 843 pairs of cases and controls,the average age of the case group was 64.62±9.94 years old,and the average age of the control group was 64.54±9.66 years old.The male subjects in the case group and the control group were 332(39.4%)respectively,and female subjects in the case group and control group were 511(60.6%)respectively.In the case and the control group,the distribution of age and gender was not significantly different(P>0.05).Drinking levels was differently distributed between the case group and the control group,the difference was statistically significant(P<0.05).Smoking and physical activity have no significant differences between the case group and the control group(P>0.05).In the case group,Systolic blood pressure,diastolic blood pressure,body mass index,fasting blood glucose,2-hour postprandial blood glucose,glycosylated hemoglobin,triglyceride,low-density lipoprotein and total cholesterol were higher compared to the control group,the difference was statistically significant(P<0.05).The high density lipoprotein in the case group was lower than that of the control group,the difference was statistically significant(P<0.05).(2)The genotype frequency distribution of rs6573769,rs3810610 and rs13515 in the control group consistent with Hardy-Weinberg genetic equilibrium(P >0.05).In the case group and the control group,the three SNPs alleles and genotype frequencies of EIF2S1 gene and MAPK1 gene were not significantly different(P>0.05),respectivily.Subjects carrying the CC genotype of rs6573769 had a higher risk of developing T2 DM than those carrying the TT and TC genotypes in the recessive model(P=0.037).After adjusting for smoking,drinking,and BMI.Subjects carrying the CC genotype still had a higher risk of developing T2 DM than those carrying TT and TC genotypes(OR=1.283,95% CI=1.022-1.611,P=0.032).Rs3810610 and rs13515 were not found to be associated with type 2 diabetes in the codominant model,the dominant model and the recessive model,respectively.(3)In the study population,after adjusting for smoking,drinking and BMI,we found that subjects with TT genotype had a significant higher 2h PBG levels than subjects carrying genotype CC in the codominant model of rs13515(P=0.039);In the recessive model of rs13515,subjects carrying the TT genotype had a higher 2h PBG levels than subjects with CC and TC genotypes,and the difference was statistically significant(P=0.035).rs6573769 and rs3810610 polymorphisms have no association with metabolism indicators.(4)The haplotype analysis was performed rs3810610 and rs13515 on MAPK1 gene.The distribution of the three haplotypes was not found to be associated with T2 DM in the case group and control group(P>0.05).(5)Using the generalized multi-factor dimensionality reduction method to analyze the interaction of gene-gene and gene-environmental factors.In the genegene interaction results,there was an interaction between rs6573769 and rs13515 in the two-factor model(P=0.011).However,there was no significant interaction between EIF2S1 and MAPK1 genes and environmental factors.Conclusions:(1)The CC genotype of EIF2S1 gene rs6573769 may increase the risk of T2 DM.(2)In the study population,the TT genotype of the rs13515 of the MAPK1 gene may be associated with a higher 2h PBG level.(3)The interaction between EIF2S1 gene and MAPK1 gene revealed that there was an interaction between rs6573769 and rs13515,which may increase the risk of type 2 diabetes.