Association Between SLC22A1, SLC22A4 Gene Polymorphisms And Metformin Therapeutic Efficacy In Type 2 Diabetes Melitusiabetes Mellitus

Objective This study aimed to evaluate the correlation of SLC22A1 rs628031 and SLC22A4 rs272893 polymorphisms with metformin efficacy in type 2 diabetes mellitus(T2DM) patients.Methods This study selected 300 T2 DM patients and 298 healthy subjects to detect allele frequencies of rs628031 and rs272893 polymorphisms(SNPs) among Han Chinese population in Gansu.Genotypes of the 2 SNPs in all selected person were identified by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP).One hundred and five newly diagnosed T2 DM patients were took metformin monotherapy(500mg/d)for 90 consecutive days.、The subjects were divided into different groups according to genotypes of the two SNPs and to analyze the relationships between the each genotype and the changes of the fasting plasma glucose(FPG), 2h postprandial glucose(PPG-2h) and glycosylated hemoglobin HbA1c%.Results In T2 DM patients of Han nationality in Gansu of China, SLC22A1 rs628031 AA genotype was counted for 11.4%, AG genotype was 42.3%, GG genotype was 46.3%, A allele frequency was 32.5%, G allele frequency was 67.5%. In healthy control population, SLC22A1 rs628031 AA genotype was 8.4%, AG genotype was 44.3%, GG genotype was 47.3%, A allele frequency was 30.7%, G allele frequency was 69.3%. Chinese in Gansu Han T2 DM patients, SLC22A4 rs272893 AA genotype was accounted for 31.3%, AG genotype was accounting for 52.7%, GG genotype was accounted for 16%; the frequency of A allele was 57.7%, the frequency of G allele was 42.3%. A group of healthy people, the SLC22A4 rs272893 AA genotype was accounted for 32.7%, AG genotype was accounting for 50%, GG genotype was accounted for 17.3%; the frequency of A allele was 57.7%, the frequency of G allele was 42.3%. Allele frequency of the two SNPs were no significant difference between Chinese Gansu Han T2 DM patients and healthy controls(p>0.05).T2DM patients treated in the metformin. After 90 days later, the decrease of FPG of AG genotype is higher than AA genotype(AG genotype FPG: before treatment-10 ±2.74, after treatment-7.39±1.27, p<0.05) and the decrease of HbA1c% of AG genotype genotype was higher than AA genotype(AG gene type HbA1c%: before treatment-9.24±2.43, after treatment-7.09±1.13, p<0.05); GG gene type’s FPG decreased compared with the AA genotype(GG genotype FPG: before treatment-9.80 ±3.19, after treatment-6.89±1.29, p<0.05) and HbA1c% of GG genotype decreased compared with AA genetype(GG FPG genotype: before treatment-8.80±2.42, after treatment-6.85±1.24, p<0.05); and the mutation G in genotype homozygote, FPG decreased more significantly, G in genotype in hybridity, HbA1c% decreased more significantly, the genotype of AG and GG genotypes Compared with FPG and HbA1c% decreased the difference was not significant; while the PPG-2h before and after treatment changes in the range among the 3 groups were not statistically significant. T2 DM patients treated in the metformin. After 90 days later, the decrease of FPG of AG genotype is higher than AA genotype(GG genotype FPG: before treatmen-9.80± 3.19, after treatment-689±1.29, P < 0.05), No statistically significantly difference was found between AA genotype and AG genotype for FPG; PPG-2h and HbA1c% in amplitude change before and after treatment among the 3 groups had no statistical significance.Conclusions SLC22A1 rs628031 and SLC22A4 rs272893 polymorphisms were associated with metformin efficacy in T2 DM patients.