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

Diabetes Obes Metab. 2013 Feb;15(2):189-91. doi: 10.1111/j.1463-1326.2012.01691.x. Epub 2012 Sep 9.

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 6 months. 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.

MeSH terms

  • Alleles
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Genotype
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Male
  • Metformin / pharmacology*
  • Middle Aged
  • Organic Cation Transport Proteins
  • Polymorphism, Single Nucleotide*
  • Treatment Outcome

Substances

  • Hypoglycemic Agents
  • Organic Cation Transport Proteins
  • SLC47A1 protein, human
  • Metformin