Association of genetic variation in the organic cation transporters OCT1, OCT2 and multidrug and toxin extrusion 1 transporter protein genes with the gastrointestinal side effects and lower BMI in metformin-treated type 2 diabetes patients

Linda Tarasova, Ineta Kalnina, Kristine Geldnere, Alda Bumbure, Rota Ritenberga, Liene Nikitina-Zake, Davids Fridmanis, Iveta Vaivade, Valdis Pirags, Janis Klovins

Research output: Contribution to journalArticlepeer-review

89 Citations (Scopus)

Abstract

OBJECTIVE: Metformin is the most widely used oral antidiabetic drug for the treatment of type 2 diabetes (T2D). So far, the number of polymorphisms in SLC22A1, SLC22A2, and SLC47A1 genes coding for organic cation transporter 1 (OCT1), OCT2, and multidrug and toxin extrusion transporter 1 (MATE1) metformin transporters have been described in association with the efficacy of metformin. However, there is no information on the influence of genetic variations within these genes on the side effects of metformin. In this study, we assessed whether five single-nucleotide polymorphisms and two indel polymorphisms are associated with the side effects of metformin in patients with T2D. METHODS: Seven polymorphisms in OCT1, OCT2, and MATE1 genes were compared between 53 T2D patients with side effects of metformin and 193 metformin users without symptoms of metformin intolerance. RESULTS: We found a statistically significant association between the A allele of the rs628031 (P=0.012, odds ratio=0.389, confidence interval 95% [0.186-0.815]) as well as 8 bp insertion (rs36056065) in the OCT1 gene (P=0.002, odds ratio=0.405, confidence interval 95% [0.226-0.724]) and the presence of the side effects of metformin. CONCLUSION: Two genetic variations in OCT1 that are in strong linkage disequilibrium may predispose toward an increased prevalence of the side effects of metformin in patients with T2D.

Original languageEnglish
Pages (from-to)659-666
Number of pages8
JournalPharmacogenetics and Genomics
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 2012
Externally publishedYes

Keywords*

  • Antidiabetic
  • biguanides
  • body mass index
  • HbA1c
  • pharmacogenetics
  • single-nucleotide polymorphism

Field of Science*

  • 1.6 Biological sciences
  • 3.1 Basic medicine
  • 3.2 Clinical medicine

Publication Type*

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

Fingerprint

Dive into the research topics of 'Association of genetic variation in the organic cation transporters OCT1, OCT2 and multidrug and toxin extrusion 1 transporter protein genes with the gastrointestinal side effects and lower BMI in metformin-treated type 2 diabetes patients'. Together they form a unique fingerprint.

Cite this