Polymorphisms of angiotensin-converting enzyme (ACE) and ACE2 are not associated with orthostatic blood pressure dysregulation in hypertensive patients

Abstract

Aim: The genetic background of orthostatic blood pressure dysregulation remains poorly understood. Since the renin-angiotensin system plays an important role in blood pressure regulation and response to position change, we hypothesized that angiotensin-converting enzyme (ACE) and ACE2 genetic polymorphisms might contribute, at least partially, to orthostatic blood pressure dysregulation in hypertensive patients. Methods: Two tag single nucleotide polymorphisms (SNPs) of ACE2 and ACE I/D were genotyped in 3630 untreated hypertensive patients and 826 normotensive subjects. Orthostatic hypertension was defined as an increase in systolic blood pressure of 20 mmHg or more and orthostatic hypotension as a drop in blood pressure of 20/10 mmHg or more within three minutes of assumption of upright posture. Results: Female and male patients had similar rates of orthostatic hypertension (16.5% vs 15.3%) and hypotension (22.5% vs 23.8%). No significant differences were detected in the minor allele frequency of ACE2 rs2106809, rs2285666, or ACE I/D in either female or male patients with orthostatic hypertension (15.1%, 22.7%, 19.6%, respectively), hypotension (13.8%, 25%, 16.5%), or normal orthostatic blood pressure response (14.4%, 21.9%, 15.8%) in additive, dominant or recessive models after adjustment for confounders (all P>0.05). The orthostatic changes in systolic and diastolic blood pressure were also comparable among patients carrying different genotypes. Similar results were observed in normotensive subjects. Conclusion: These data provide no support for the involvement of ACE or ACE2 in the genetic predisposition to orthostatic hypotension or hypertension.

Association of angiotensin-converting enzyme and angiotensin-converting enzyme-2 gene polymorphisms with essential hypertension in the population of Odisha, India

“…Because ACE and ACE2 act in counteracting ways (Crackower et al, 2002;Fan et al, 2009) we tested for any possible association, but, in our study no combined effect of ACE I/D and ACE2 rs2106809 polymorphisms was observed. Fan et al (2007), however, reported that ACE2 rs2106809 T allele when combined with the effect of the ACE DD genotype, increased the risk for hypertension by 2.34-fold in females.…”

“…Chen et al (2010), in China, found the rs2106809 polymorphism to be associated with pulse pressure in women and men and with reduction in systolic blood pressure in women and also that it might act as an independent influencing factor of gene-gene interaction in BP reducing effects of benazepril. Fan et al (2009), however, did not find any significant association in either female or male Chinese patients with orthostatic hypertension. There are also some other studies on polymorphisms which did not show gender specification.…”

“…To our knowledge, this is the first study regarding ACE I/D polymorphism in relation to hypertension in the state of Odisha (India) and ACE2 rs2106809 in India. ACE and ACE2 both play an important role in BP regulation and act in a counteracting fashion to maintain a normal blood pressure level in the human body (Fan et al, 2009). Therefore, studies have been conducted to analyse mutations in these two genes which may predispose to hypertension.…”

“…ACE2 hydrolyses angiotensin II to angiotensin 1-7 which is a vasodilator and partially hydrolyses angiotensin I (Tipnis et al, 2000). ACE2 rs2106809 mutation (C!T) has been reported to be associated with clinical manifestation of hypertension (Chen et al, 2010;Fan et al, 2009). However, no report in this aspect is available in India.…”

The association between angiotensin-converting enzyme 2 polymorphisms and essential hypertension risk: A meta-analysis involving 14,122 patients

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] However, the results from these studies were inconsistent.…”