Study On Correlation Of Genetic Polymorphism Of PRKAA2 With Metformin Response

Objective: To study the single nucleotide polymorphism (SNPs) of AMP-activated protein kinase (AMPK)α2 subunit gene PRKAA2(rs2051040 and rs17848595) and its relationship with metformin response. To observe the effects of metformin on the serum levels of true insulin, adiponectin, leptin, resistin and lipopolysaccharide. Methods: A total of 32 patients with type 2 diabetes (T2DM) were enrolled through a standard. All patients were required to take for metformin 1 week. FPG, TG, TC, LDL-C, HDL-C were assayed before and after therapy and the induced rate of FPG were calculated to assess the therapeutic effects of metformin. The gene polymorphism of PRKAA2 was analyzed by PCR-DGGE, the effects of were metformin compared between patients with different phenotypes. Twenty patients were continued use metformin on equal dose until fourth week. The serum level of true insulin, adiponectin, leptin and resistin were analyzed by ELISA before and after treatment with metformin. Results: 1) Patients with T2DM have 3 genotypes in both groups. 2) The serum level of FPG, TG, TC, LDL-C were significantly improved in wide type genotypes after with metformin one week(P<0.05). The change of index were no significantly different in mutate genotype groups after therapy with metformin( P>0.05). 3) After four weeks treatment, the level of adiponectin was increased, level of leptin and HOMA-index were decreased, no change in insulin, and resistin. 4)rs2050140 SNP have relation to the effect of metformin on adiponectin, rs17848595 SNP have relation to the effect of metformin on leptin. Conclusion:The polymorphism of rs2051040 and rs17848595 in PRKAA2 have associated with metformin response. Metformin can improve insulin sensitivity, advance adiponectin, lower leptin, no effect on resistin level.