| ObjectiveTo investigate the relationship between Glucose-6-phosphatase catalytic subunit2(G6PC2)gene polymorphism and the susceptibility of type 2 diabetes mellitus(T2DM)in Chinese rural populations,and the effects of gene-gene,gene-obesity related indicators interactions on T2DM.MethodsThe subjects of our study were all from the"Chinese rural population cohort study".We selected 538 subjects who developed incident T2DM during the follow-up as the case group,controls were matched in a 1:1 ratio to cases by age(within 2years),sex,village,marital status.Whole blood genomic DNA was extracted by magnetic bead adsorption method,and the G6PC2 gene rs492594,rs16856187 and rs13387347 were genotyped by SNPscanTM multiple single nucleotide polymorphism(SNP)typing kits.Mann-Whitney U test and?~2 test were used to analyze the distribution of continuous variables and categorical variables.The conditional logistic regression model was used to evaluate the effect of G6PC2 gene polymorphisms on the risk of T2DM;The conditional logistic regression model,Rothman and Hosmer compiled software were used to analyze the multiplicative and additive interaction between loci and Body Mass Index(BMI)or Waist-height ratio(WHtR)in the development of T2DM;the linear regression was used to analyze the associations between loci and glucose metabolism related characteristics.All the analysis was performed using SPSS 21.0.The haplo.stats package in R was applied to assess the haplotype of rs492594,rs16856187 and rs13387347 loci and their relation with T2DM susceptibility.ResultsA total of 1076 subjects were enrolled in this study,including 538 new-onset T2DM patients and 538 controls.There were 195 males and 343 females in the case and control groups,respectively.1.Compared with non-T2DM group,the value of BMI,WHtR,systolic blood pressure,diastolic blood pressure,pulse pressure difference,fasting plasma glucose(FPG),Total cholesterol(TC),Triglyceride(TG)levels in T2DM group were higher,but high density lipoprotein cholesterol(HDL-C)level is a lower.The distribution of dyslipidemia and family history of diabetes was statistically significant between the two groups(P<0.05).2.The genotype and allele frequency distribution of rs492594,rs16856187 and rs13387347 were not statistically different between T2DM and control groups.After adjustment for age,gender,BMI,smoking,alcohol consumption,physical activity,family history of diabetes,and dyslipidemia,for rs492594,compared with those carrying the GG genotype,under the additive model,those who carrying the CG genotype can decrease the risk of T2DM(OR=0.550,95%CI=0.348-0.868);under the dominant model,the population carrying the CG and CC genotypes also decrease the risk of T2DM(OR=0.589,95%CI=0.384-0.904),both of which were significant(P<0.05).For rs13387347,in the recessive model,the risk of T2DM in the population who carrying CC genotype was(1.759(1.050-2.946),P=0.032)when compared with those carrying the CT and TT genotypes.However,there was no statistical correlation between rs16856187 and T2DM risk in each genotype model(P>0.05).3.Analysis about haplotypes showed that there was no statistical correlation between the haplotypes of CAT,CAC,GAC,GAT,GCC,GCT and T2DM(P>0.05).However,the corrected total score tests of six haplotypes were statistically significant(P=0.034).4.There was no statistically significant interaction between G6PC2 gene and BMI or WHtR on T2DM.5.After adjustment for age,gender and BMI,the results showed that only rs492594-C allele was associated with higher FPG at follow-up and the change of FPG during follow-up.With each additional C allele,FPG decreased by 0.232mmol/L and the change of FPG increased by 0.208 mmol/L.Conclusions1.In Chinese rural population,rs492594 G and rs13387347 C allele in the G6PC2 gene may increase the risk of T2DM.2.No interaction was found between the rs492594,rs16856187,and rs13387347loci.3.No interaction was found between G6PC2 gene and BMI or WHtR. |
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