Association study of ACE2 (angiotensin I-converting enzyme 2) gene polymorphisms with coronary heart disease and myocardial infarction in a Chinese Han population

Abstract

Results are accumulating that ACE2 (angiotensin I-converting enzyme 2) might act as a protective protein for cardiovascular diseases; however, only a few studies in human populations have been carried out. This prompted us to perform a case-control study to investigate the relationship of ACE2 polymorphisms with CHD (coronary heart disease) and MI (myocardial infarction). Three single nucleotide polymorphisms in the ACE2 gene (1075A/G, 8790A/G and 16854G/C) were genotyped by PCR-RFLP (restriction-fragment-length polymorphism) in 811 patients with CHD (of which 508 were patients with MI) and 905 normal controls in a Chinese population. The polymorphisms were in linkage disequilibrium (r(2)=0.854-0.973). Analyses were conducted by gender, because the ACE2 gene is on the X chromosome. In females, an association was detected with MI for 1075A/G (P=0.026; odds ratio=1.98) and 16854G/C (P=0.028; odds ratio=1.97) in recessive models after adjusting for covariates. In male subjects, two haplotypes (AAG and GGC) were common in frequency. In male subjects not consuming alcohol, the haplotype GGC was associated with a 1.76-fold risk of CHD [95% CI (confidence interval), 1.15-2.69; P=0.007] and a 1.77-fold risk of MI (95% CI, 1.12-2.81; P=0.015) with environmental factors adjusted, when compared with the most common haplotype AAG. In conclusion, the results of the present study indicate that common genetic variants in the ACE2 gene might impact on MI in females, and may possibly interact with alcohol consumption to affect the risk of CHD and MI in Chinese males.

Sex and the renin-angiotensin system: inequality between the sexes in response to RAS stimulation and inhibition

“…Within the RAS, genetic polymorphisms in ACE, angiotensinogen, and the AT 1 receptor have been more closely linked with the development of cardiovascular complications in men (25,79). In contrast, a strong association has been found for the ACE2 gene A/G polymorphism at nucleotide 8790 in intron 3 with hypertension in female Chinese patients with metabolic syndrome and myocardial infarction, with no association in men (83,86). These findings make it tempting to speculate that ACE2 may play a larger role in modulating cardiovascular-renal health in women, although, in ACE2 knockout mice, males develop severe renal injury with age, while female mice do not (50).…”

Role of ACE2 in diastolic and systolic heart failure

“…Increased production of superoxide, activation of matrix metalloproteinases, and pathological signaling leads to the severe adverse myocardial remodeling and dysfunction in ACE2KO mice [7]. Single nucleotides polymorphisms (SNPs) of ACE2 are associated with variation in left ventricular mass, septal wall thickness and ventricular hypertrophy [35], coronary heart disease and myocardial infarction [36], and hypertension in patients with metabolic syndrome [37]. Consistent with a key role of ACE2 in post-MI remodeling, overexpression of ACE2 ameliorates left ventricular remodeling and dysfunction in a rat model of myocardial infarction [38].…”

Transgenic Angiotensin-Converting Enzyme 2 Overexpression in Vessels of SHRSP Rats Reduces Blood Pressure and Improves Endothelial Function

“…22 Additionally, polymorphisms in the ACE2 gene have also been linked to the development of pathological myocardial hypertrophy and heart disease in human. 36,37 The purpose of this study was to investigate the role of ACE2 in the pathogenesis of hypertension in the SHRSP rat model. Therefore, we generated transgenic SHRSP rats with overexpression of ACE2 in vascular smooth muscle cells.…”