Assocation Between DPP-4 Gene Polymorphisms And T2DM And The Effective Treament With Sitagliptin In Patients With Type 2 Diabetes Mellitus

Objective:T2DM patients were studied to study the association between single nucleotide polymorphism of DPP-4 gene and T2DM and the effect of treatment with sitagliptin in Patients with T2DM.Methods:This study selected T2DM outpatients from Sichuan Provincial People's Hospital from July 2016 to December 2017 as the experimental group,and the healthy population of the physical examination center as the control group.Genotyping was performed using the MassArray system to determine the genotypes of the DPP-4 polymorphism SNPs(rs2160927,rs3788976,and rs 10930040)in the T2DM and control,and the chi-square test analyzed genotype differences between the two groups.According to the Nafficiency criteria,eligible T2DM subjects with poor glucose control were selected for treatment with sitagliptin(100 mg/d)for 12 weeks and genotyped for DPP-4 polymorphism SNPs(rs2160927,rs3788976,rs10930040).Age,gender,height,weight,fasting blood glucose levels,average glycohemoglobin and other physiological and biochemical indexes were collected.In accordance with the normal distribution quantitative data,the t test was used for comparison between the two groups.One-way analysis of variance was used for comparison between groups.Kruskal-Wallis H non-parametric test was not applied to the normal distribution.The correlation between DPP-4 gene polymorphism and T2DM was analyzed.Sex and its effects on the efficacy of sitagliptin in the treatment of T2DM.Results:1.Including 97 patients with T2DM,the average age was(53.30±10.76)years,the history of diabetes was(6.14±2.94)years,fasting blood glucose was(9.79±2.43)mmol/L,and glycosylated hemoglobin was(8.28±0.89)%;healthy control 36 For example,fasting blood glucose was(4.79±0.37)mmol/L,and glycated hemoglobin(5.12±0.58)%.The correlation between DPP-4 gene polymorphisms and T2DM was studied.The results showed that the distribution of DPP-4 gene SNP rs2160927,rs3788976 and rs10930040 polymorphisms in the control group was consistent with the Harvard equilibrium(P>0.05),SNP There was no strong linkage disequilibrium between;SNP rs2160927 in the allele model(OR(95%CI)= 2.059(1.097-3.867);P = 0.023),dominant model(OR(95%CI)= 2.351(1.065-5.192);P=0.032)Related to T2DM.The dominant model of SNP rs10930040(OR(95%CI)= 2.944(1.297-6.684);P=0.009)was significantly associated with T2DM.SNP rs3788976 was not found to be significantly associated with T2DM in each genetic model.2.Finally,79 patients with T2DM were treated with sitagliptin,53(67.1%)males and 26(32.9%)females;the mean age of the patients were(54.53±9.61)years;mean HbA1c(8.29±0.87)%.? SNP rs2160927,after treatment,HOMA-IR decreased significantly in TC genotypes compared with TT and CC genotypes(P=0.000),dominant model(P=0.001),recessive model(P=0.000),additive model(P= 0.000)The difference was statistically significant;TT genotype significantly decreased post-treatment glycosylated hemoglobin(P=0.023)in the recessive model,and the T allele significantly reduced post-treatment glycosylated hemoglobin compared to C allele(P=0.031);In the dominant model,the C-peptide was significantly higher in the TT + TC genotype 2 hours after the meal than in the CC genotype(P =0.022).?SNP rs3788976,compared with AA and GG genotypes,AG genotype significantly reduced the difference was statistically significant(P=0.046).Under the recessive model,AG+GG genotype decreased HbAlc significantly higher than AA gene after treatment.There was a statistically significant difference(P=0.015);in reducing fasting blood glucose,AG genotypes were significantly lower than those of AA and GG genotypes(P=0.037).Under the recessive model,AG+GG Genotype reduced fasting plasma glucose significantly higher than that of AA genotype(P=0.013);it showed similar changes to fasting glucose in terms of reducing postprandial blood glucose 2 hours,ie AG+GG genotype reduced postprandial blood glucose significantly higher than 2 hours postprandial AA genotype(P=0.036).?SNP rs 10930040,in the recessive model,the glycated hemoglobin was more significantly reduced after GG genotype reduction(P=0.023).In the allele model,the G allele decreased glycated hemoglobin protein higher than the A allele(P=0.023).;In the increase of C-peptide 2 hours after the meal,the GG+GA genotype was significantly higher than the AA genotype in the dominant model.The DPP-4 gene SNPs rs2160927,rs3788976,rs10930040 had no significant difference in DPP-4 activity and plasma GLP-1 concentration in the four genetic models.Conclusion:1.DPP-4 gene rs2160927,rs 10930040 polymorphism may be susceptibility gene of T2DM.2.DPP-4 gene rs2160927 polymorphism,C allele carrier may be related to the reduction of HbAlc in the treatment of type 2 diabetes with sitagliptin.3.DPP-4 gene rs3788976,G gene carriers may be associated with the treatment of Sitagliptin in type 2 diabetes HbAlc increase,G gene carrier may be reduced fasting plasma glucose and postprandial 2 hours blood glucose treatment with sitagliptin.4.DPP-4 gene rs 10930040,A gene carrier and sitagliptin treatment of type 2 diabetes HbAlc reduction,G gene carrier may be related to the treatment of sitagliptin increased postprandial C peptide related.