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- Title
Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea-induced hypoglycaemia: A GoDARTS Study.
- Authors
Dujic, Tanja; Zhou, Kaixin; Donnelly, Louise A.; Leese, Graham; Palmer, Colin N. A.; Pearson, Ewan R.
- Abstract
Data on the association of CYP2C9 genetic polymorphisms with sulfonylurea ( SU)-induced hypoglycaemia ( SH) are inconsistent. Recent studies showed that variants in the 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 1770 patients were included in the analysis of SU efficacy, assessed as the combined outcome of the HbA1c reduction and the 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 = .009) and better response to SU treatment (β, −0.218; SE, 0.074; P = .003) only in patients carrying the 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.
- Subjects
CYTOCHROME P-450; OXIDOREDUCTASES; HYPOGLYCEMIA; SULFONYLUREAS; GENETIC polymorphisms; DISEASE risk factors
- Publication
Diabetes, Obesity & Metabolism, 2018, Vol 20, Issue 1, p211
- ISSN
1462-8902
- Publication type
Article
- DOI
10.1111/dom.13046