Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea-induced hypoglycaemia: A GoDARTS Study

Tanja Dujic, Kaixin Zhou, Louise A. Donnelly, Graham Leese, Colin N. A. Palmer, Ewan R. Pearson (Lead / Corresponding author)

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Abstract

Data on the association of CYP2C9 genetic polymorphisms with sulfonylurea (SU)-induced hypoglycaemia (SH) are inconsistent. Recent studies showed that variants in P450 oxidoreductase (POR) gene could affect CYP2C9 activity. In this study, we explored the effects of POR*28 and combined CYP2C9*2 and CYP2C9*3 genotypes, on SH and the efficacy of SU treatment in type 2 diabetes. A total of 1,770 patients were included in the analysis of SU efficacy assessed as the combined outcome of the HbA1c reduction and prescribed SU daily dose. Sixty nine patients with severe SH were compared with 311 control patients. The number of CYP2C9 deficient alleles was associated with nearly three-fold higher odds of hypoglycaemia (OR=2.81, 95%CI 1.30-6.09, P=0.009) and better response to SU treatment (β = -0.218, SE=0.074, P=0.003) only in patients carrying POR*1/*1 genotype. Our results indicate that interaction between CYP2C9 and POR genes may be an important determinant of efficacy and severe adverse effects of SU treatment.

Original languageEnglish
JournalDiabetes, Obesity & Metabolism
Early online date28 Jun 2017
DOIs
Publication statusPublished - 25 Aug 2017

Keywords

  • hypoglycaemia
  • pharmacogenetics
  • sulphonylureas
  • type 2 diabetes

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