Pharmacogenomic association between a variant in SLC47A1 gene and therapeutic response to metformin in type 2 diabetes

Abstract

Pharmacogenetic studies revealed that variants in genes related to the pharmacokinetics of metformin were associated with glucose-lowering effect of metformin. The aim of this study was to investigate possible associations of the variants in genes encoding organic cationic transporters-solute carrier family 22, members A1, A2 (SLC22A1, SLC22A2) and solute carrier family 47, member A1 (SLC47A1) with response to metformin in type 2 diabetes. One hundred forty-eight drug-naive patients with type 2 diabetes were included in the study. Genotyping for SLC22A1 rs622342, SLC22A2 rs316019 and SLC47A1 rs2289669 variants was performed using real-time PCR with subsequent melting-curve analysis. SLC47A1 rs2289669 genotype was significantly associated with the reduction in haemoglobin A1c (HbA1c) after 6months. Twenty percentage of patients with diabetes that are homozygous for A-allele of SLC47A1 had twofold reduction in HbA1c in comparison with the patients carrying G-allele (GG+GA: 0.55±0.09% vs. AA: 1.10±0.18%, p=0.018). In conclusion, the results of this study might have in future practical implication in personalised treatment of patients with type 2 diabetes. © 2012 Blackwell Publishing Ltd.