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

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.

The association of an adenine insertion variant in the 5'UTR of the endothelin-1 gene with hypertension and orthostatic hypotension.

INTRODUCTION: An adenine insertion polymorphism in the 5' untranslated region of the endothelin-1 gene is functional and increases the expression of endothelin mRNA and protein in the insertion homozygote. In the present study we hypothesized that this functional polymorphism might be associated with hypertension and/or orthostatic hypotension. MATERIAL AND METHODS: The adenine insertion polymorphism was genotyped in 381 untreated hypertensive patients and 298 normotensive subjects, all of whom underwent an upright posture study for orthostatic blood pressure measurements. Orthostatic hypotension was defined as a drop in blood pressure of 20/10 mm Hg or more within 3 min of assuming the upright posture. RESULTS: The allele frequency of the adenine insertion was similar in hypertensive and normotensive subjects (15.2% vs. 15.3%, p > 0.05). After adjustment for age, sex and body mass index, blood pressure levels did not differ significantly among the genotypes in both hypertensives and normotensives. No associations were found between the distribution of the adenine insertion genotypes and the risk of orthostatic hypotension in both hypertensive patients and normotensive subjects even after adjustment for demographic parameters and supine systolic or diastolic blood pressure. Neither hypertensive nor normotensive subjects showed significant differences in orthostatic systolic or diastolic blood pressure changes among the genotype groups (all p > 0.05). CONCLUSIONS: We concluded that the functional adenine insertion polymorphism in the endothelin-1 gene is not associated with either hypertension or orthostatic hypotension risk in Chinese.