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

KEYWORDS::

• Brazilian population
• hydralazine
• NAT2 polymorphism
• resistant hypertension
• SNP

Acknowledgements

The authors wish to thank the sequencing PDTIS-FIOCRUZ and Bioinformatics Platforms for their support.

Financial & competing interests disclosure

The study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 400148/2011-0, the Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), the Oswaldo Cruz Institute (FIOCRUZ) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The study was supported by research grants from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 400148/2011-0, the Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ), the Oswaldo Cruz Institute (FIOCRUZ) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.