Relationship Between The SNP-rs11212617 (C/A) Locus And The Therapeutic Effect Of Metformin On Diabetes Patients With Type 2 Diabetes Mellitus

Objective:To investigate the effect of rs11212617 polymorphism of ataxia telangiectasia-mutated gene(ATM)gene on the therapeutic of metformin and to explore the genetic mechanism affecting the efficacy of metformin.Methods:Sixty patients newly diagnosed with type 2 diabetes in the affiliated people’s hospital of jiangsu university were selected and treated with metformin with the dosage of 1000 mg daily for 12 weeks.The fasting plasma glucose(FPG)、2 hours postprandial blood glucose(2h PG)were detected at baseline and after being treated with metformin for 4 weeks and 12 weeks,respectively.Meanwhile,the totalcholesterol(TC),triglyceride(TG),low density lipoprotein-cholesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C)level and Hb A1 c were measured in serum before and after treatment.The patients’ DNA was extracted to detect the genotype of ATM gene SNP-rs11212617(C/A)and the patients were divided into groups according to their genotypes.Pearson correlation analysis and multivariate linear regression analysis were used to analyze the factors that affect the efficacy of metformin.Results:PCR-PFLPS and agarose gelelectrophoresis showed that there were three genotypes in rs-11212617 polymorphism of ATM gene,which were divided into three groups: AA group,CC group and AC group.There were no significant difference in FPG,2h PG,Hb A1 c and the baseline data among three groups(P>0.05).The FPG,2h PG and Hb A1 c decreased significantly after 12 weeks of treatment with metformin(all P<0.05).The FPG,2h PG and Hb A1 c level were remarkly lower in AA genotype group compared with AC genotype group and CC genotype group after treated with metformin for 12 weeks(all P<0.05).The Δ FPG,Δ2h PG and ΔHb A1 c level were remarkly higher in AA genotype group compared with AC genotype group and CC genotype group after treated with metformin for 12 weeks(all P<0.05).BMI,TC,TG,LDL-C at baseline were negatively related to Δ2h PG.The dose of metformin(stable treatment),Hb A1 c and HDL-C were positively correlated with Δ2h PG.Multivariate linear regression analysis(stepwise)showed that SNP-rs11212617 genotype,metformin dose and Hb A1 c were important factors in patients with Δ2h PG.Conclusion:(1)The study provides evidence that rs11212617 polymorphism of the ATM gene could be found in the Han population who were newly diagnosed type 2 diabetes.(2)ATM-rs11212617 gene polymorphism was associated with the therapeutic effect of metformin.T2 DM patients with AA genetype may be more sensitive to metformin than those with AC and CC genotype.