The Genetic Polymorphisms of rs161620 and rs2229611 in G6PC 3'UTR Are Associated With Metformin Efficacy in Chinese Type 2 Diabetes Mellitus

Abstract

Metformin is a classical oral hypoglycemic drug, often recommended as the first-line therapy for type 2 diabetes mellitus (T2DM). Previous research has shown that the efficacy of metformin is associated with the genetic polymorphisms of patients. Considering the role of G6PC in gluconeogenesis and glycogenolysis, this study aims to investigate the association of G6PC rs161620 and rs2229611 with metformin efficacy in T2DM patients who take metformin only. According to the decrease of HbA1c, 116 T2DM patients receiving metformin monotherapy were divided into two groups: response group (the decrease of HbA1c by at least 1.5% after 3 months) and non-response group (the decrease of HbA1c < 1.5%). SNPscan technology was used to genotype. There were significant differences in rs161620 and rs2229611 presented in genotype frequency (p = 0.027 both) between the response group and the non-response group. According to the results of logistic analysis, the genetic polymorphisms of G6PC rs161620 or rs2229611 could influence the hypoglycemic effect of metformin in T2DM patients. We found that the decreasing values of PBG and HbA1c in G6PC rs161620 (C > A) or rs2229611 (T > C) mutants were significantly more than those in wild-type individuals, which means the more effective genotypes of metformin are CA/AA of rs161620 and TC/CC of rs2229611. This study suggested that the G6PC rs161620 and rs2229611 genetic polymorphisms were significantly associated with metformin efficacy in Chinese T2DM patients.

Keywords: G6PC; metformin; polymorphism; rs161620; rs2229611; type 2 diabetes mellitus.

FIGURE 1

The decreases of PBG value and HbA1C value in T2DM patients after metformin treatment. (a) the decrease of PBG value in G6PC rs161620 (C >A ) mutants was significantly greater than that in wild‐type individuals. (b) the decrease of HbA1c value in G6PC rs161620 (C > A) mutants was significantly greater than that in wild‐type individuals. (c) the decrease of PBG value in G6PC rs2229611 (T > C) mutants was significantly greater than that in wild‐type individuals. (d) the decrease of HbA1c value in G6PC rs2229611 (T >C ) mutants was significantly greater than that in wild‐type individuals. Data are shown as mean ± SD. *p < 0.05 compared with the wild type (n = 116). **p < 0.01 compared with the wild type (n = 116).