Impact of ACE2 gene polymorphism on antihypertensive efficacy of ACE inhibitors

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Abstract

Angiotensin-converting enzyme 2 (ACE2), a newly discovered member of renin–angiotensin–aldosterone system, counterbalances the actions of angiotensin-converting enzyme. The objective of our study was to assess the association between rs2106809 polymorphism in ACE2 gene and the blood pressure response to ACE inhibitors in untreated hypertensive patients. After a 2-week, double-blind placebo run-in period, either benazepril or imidapril was administered for 6 weeks to 497 patients with mild to moderate essential hypertension. The achieved changes in BP were analyzed for their association with genotypes at ACE2 gene loci. In female hypertensive patients, the genotype frequency of ACE2 rs2106809 was 36.7%, 45.2% and 18.1% for CC, CT and TT genotypes, respectively. After 6 weeks of treatment, the reductions in diastolic blood pressure were significantly greater in female patients carrying the CC or CT genotype compared with those carrying the TT genotype (9.62±6.83 or 10.2±7.2 versus 6.81±6.31 mm Hg, respectively; P=0.045, analysis of variance (ANOVA)). Moreover, the reductions in mean arterial pressure were significantly greater in female patients carrying the CC or CT genotype compared with those carrying the TT genotype (12.1±7.5 or 12.0±7.9 versus 8.38±6.83 mm Hg, respectively; P=0.035, ANOVA). In male hypertensive patients, the genotype frequency of ACE2 rs2106809 was 58.1% and 41.9% for C and T genotypes, respectively. However, no association could be observed in males. We conclude that ACE2 rs2106809 is an important predictive factor of the response to antihypertensive treatment with ACE inhibitors in Chinese female hypertensive patients.

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Acknowledgements

We thank Xiangfeng Dou (Department of Epidemiology, Beijing Center for Disease Prevention and Control, Beijing, People's Republic of China) for his help in statistical analysis. This study was supported by National Natural Science Foundation of China (Nos 81273599 and 81370362); Guangdong Natural Science Foundation (No. 2015A030313661); Science and Technology Planning Project of Guangdong Province (No. 2014A020212404); National Major Research Plan Training Program (No. 91339108); and the National Basic Research Program of China (No. 2014CB542300).

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Correspondence to L J Jin or H M Yu.

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