Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea-induced hypoglycaemia: A GoDARTS Study.
Tanja DujicKaixin ZhouLouise A DonnellyGraham LeeseColin N A PalmerEwan R PearsonPublished in: Diabetes, obesity & metabolism (2017)
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.
Keyphrases
- type diabetes
- end stage renal disease
- ejection fraction
- newly diagnosed
- chronic kidney disease
- prognostic factors
- peritoneal dialysis
- machine learning
- cardiovascular disease
- emergency department
- dna methylation
- oxidative stress
- drug induced
- high glucose
- combination therapy
- deep learning
- transcription factor
- endothelial cells
- electronic health record
- bioinformatics analysis