Different phenotypes of the NAT2 gene influences hydralazine antihypertensive response in patients with resistant hypertension

Abstract

Aim: Hydralazine, a vasodilator used in resistant hypertension (RH) treatment is metabolized by an acetylation reaction mediated by N-acetyltransferase 2, the activity of which depends on NAT2 polymorphisms. Our aim was to evaluate whether different acetylation phenotypes influenced the antihypertensive effect of hydralazine in patients with RH. Patients & methods: DNA samples from 169 RH patients using hydralazine were genotyped by sequencing the NAT2 coding region, and acetylation phenotypes were defined. Results: Sixty-five patients (38.5%) were intermediate, 60 (35.5%) slow and 21 (12.4%) fast acetylators. Twenty-three (13.6%) patients were indeterminate. Upon association analysis, only slow acetylators had significant blood pressure reductions after hydralazine use, with mean 24-h systolic and diastolic blood pressure reductions of 9.2 and 5.5 mmHg. Four patients presented hydralazine adverse effects resulting in drug withdrawal, three of them were slow acetylators. Conclusion: The slow acetylation phenotype, determined by polymorphisms within NAT2, influenced both the antihypertensive and adverse effects of hydralazine in RH. Original submitted 31 May 2013; Revision submitted 7 October 2013