Acta Pharmacologica Sinica (2009) 30: 1237–1244; doi: 10.1038/aps.2009.110; published online 17 August 2009

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 ACE 2 in the genetic predisposition to orthostatic hypotension or hypertension.

Keywords: orthostatic hypotension; hypertension; angiotensin-converting enzyme; polymorphism