European Journal of Clinical Pharmacology

, Volume 71, Issue 1, pp 59–63

A pharmacogenetic association between a variation in calpain 10 (CAPN10) gene and the response to metformin treatment in patients with type 2 diabetes

  • Ivan Tkáč
  • Martin Javorský
  • Lucia Klimčáková
  • Jozef Židzik
  • Igor Gaľa
  • Eva Babjaková
  • Zbynek Schroner
  • Mária Štolfová
  • Hana Hermanová
  • Viera Habalová
Pharmacogenetics

DOI: 10.1007/s00228-014-1774-y

Cite this article as:
Tkáč, I., Javorský, M., Klimčáková, L. et al. Eur J Clin Pharmacol (2015) 71: 59. doi:10.1007/s00228-014-1774-y

Abstract

Purpose

The aim of the present study was to investigate possible associations of the single-nucleotide variants in six genes encoding the key molecules mediating the metformin pharmacodynamic effect with the response to treatment with metformin in patients with type 2 diabetes.

Methods

One hundred forty-eight drug-naïve patients with type 2 diabetes were included in the study. PRKAA1 rs249429, STK11 rs741765, PCK1 rs4810083, PPARGC1A rs10213440, HNF1A rs11086926, and CAPN10 rs3792269 variants were genotyped. The outcomes of the study were treatment success defined by achieving HbA1c <7 % and absolute reduction in HbAlc after 6-month metformin therapy. The relationships between genotypes and outcomes were evaluated in multivariate logistic and linear models. The level of statistical significance after Bonferroni correction was predefined as p < 0.0083.

Results

The minor G-allele of CAPN10 rs3792269 A > G polymorphism was significantly associated with less treatment success with an odds ratio of 0.27 (95 % CI 0.12–0.62, p = 0.002) per variant allele. When the reduction in HbA1c was analyzed as a quantitative trait, G-allele was nominally associated with a smaller reduction in HbA1c (per allele β = −0.26, 95 % CI −0.50 to −0.02, p = 0.032). The reduction in HbA1c in minor allele carriers (24 % of study population) was smaller by 0.3 % in comparison with the major allele homozygotes.

Conclusions

The present study provides the first observation of an association between a variant in CAPN10 gene and the response to metformin therapy in patients with type 2 diabetes. This observation needs to be replicated in further studies in different populations.

Keywords

Metformin Pharmacogenetics Type 2 diabetes mellitus Calpain 10 

Supplementary material

228_2014_1774_MOESM1_ESM.docx (12 kb)
ESM 1(DOCX 11 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ivan Tkáč
    • 1
    • 2
  • Martin Javorský
    • 1
    • 2
  • Lucia Klimčáková
    • 3
  • Jozef Židzik
    • 3
  • Igor Gaľa
    • 1
    • 2
  • Eva Babjaková
    • 1
    • 2
  • Zbynek Schroner
    • 1
  • Mária Štolfová
    • 1
  • Hana Hermanová
    • 3
  • Viera Habalová
    • 3
  1. 1.Department of Internal Medicine 4, Faculty of MedicineP. J. Šafárik UniversityKošiceSlovakia
  2. 2.Department of Internal Medicine 4L. Pasteur University HospitalKošiceSlovakia
  3. 3.Department of Medical Biology, Faculty of MedicineP. J. Šafárik UniversityKošiceSlovakia

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