ACE2 gene polymorphism and essential hypertension: an updated meta-analysis involving 11,051 subjects

Abstract

The polymorphisms of angiotensin-converting enzyme 2 (ACE2) gene have been suggested to be linked to increase risk of essential hypertension in multiple populations. However, the results are still debatable. To assess the association between ACE2 G8970A genetic polymorphism and essential hypertension, we conducted a meta-analysis of case-control studies across different ethnicity. PubMed, Embase, CBM, Wanfang and VIP databases were searched, and a total of 11 separate studies in females and nine separate studies in males met the inclusion criteria. Because ACE2 is on the X chromosome, data for each sex were analyzed separately. The selected studies contained 7,251 (4,472 females/2,779 males) hypertensive patients and 3,800 (2,161 females/1,639 males) normotensive controls. A statistically significant association was observed between the G8970A gene polymorphism and essential hypertension risk in female hypertensive group in the recessive genetic model (AA vs. GG+GA: P = 0.03, OR = 1.15, 95% CI = 1.02-1.30, P(heterogeneity) = 0.40, I(2) = 5%, fixed-effects model). Although no association was shown between the frequency of the A allele and the genetic susceptibility to essential hypertension in all male patients (A Allele: P = 0.38, OR = 1.10, 95% CI = 0.89-1.38, P(heterogeneity) = 0.02, I(2) = 56%, random-effects model), we found that the relationship between carrier of A allele and the essential hypertension risk in Han-Chinese male patients subgroup (A Allele: P = 0.006, OR = 1.21, 95% CI = 1.06–1.38, P(heterogeneity) = 0.10, I(2) = 44%, fixed-effects model). The current meta-analysis provided solid evidence suggesting that ACE2 gene polymorphism G8790A was probably a genetic risk factor for essential hypertension across different ethnic populations in female subjects and in Han-Chinese male subjects.

Genetic Variants Associated With Development of TMD and Its Intermediate Phenotypes: The Genetic Architecture of TMD in the OPPERA Prospective Cohort Study

“…In accordance with the function of the renin-angiotensin system in regulating blood pressure and fluid balance, numerous studies have attributed genetic differences in risk of hypertension to variation in ACE2 , 44 although no studies have reported association with any pain or sensory symptoms. Angiotensin related peptides have been posited as neurotransmitters in the periaqueductal gray 55 and other pain relevant brain areas, where they modulate pro-and anti-nociceptive pathways.…”

ACE2: Angiotensin II/Angiotensin-(1–7) Balance in Cardiac and Renal Injury

“…An increasing body of evidence suggests that ACE2 gene polymorphisms were associated with left ventricular hypertrophy (41–44), coronary heart disease and myocardial infarction (45), cardiac remodeling and urinary protein level in men with type 2 diabetes and coronary heart disease (46) as well as with hypertension (42;47;48), hypertension in women (49) and antihypertensive response to ACE inhibitors in women (50). On the other hand, some reports found no association between ACE2 and hypertension (51;52) and ACE2 and a risk for sudden cardiac death in women or men (53) underlining the necessity for further evaluation of the impact of ACE2 gene variants on cardiovascular disease in human population.…”

Angiotensin converting enzyme 2 and atherosclerosis

“…A meta-analysis of caseecontrol studies across different ethnicities, including 7251 hypertensive patients and 3800 normotensive controls, suggests that ACE2 gene polymorphism G8790A is probably a genetic risk factor for essential hypertension across different ethnic populations in female subjects and in HanChinese male subjects [39]. Whether this polymorphism contributes to the risk of atherosclerosis development is yet to be investigated although it has not been highlighted in genome wide association studies which have been currently published.…”