Relationship between genetic variants of ACE ACE 2 gene and circulating levels of ACE ACE 2 and its metabolites

摘要

Summary What is known Angiotensin‐converting enzyme 2 ( ACE 2) plays an important role in the development of essential hypertension ( EH ). Genetic factors remarkably influence circulating ACE 2 level. Objective Because heritability had remarkable effects on circulating ACE 2, we designed this study to shed light on whether circulating levels of ACE 2, angiotensin‐(1‐7) and angiotensin‐(1‐9) were linked to single nucleotide polymorphisms ( SNP s) and haplotypes in ACE 2 gene. Methods A total of 213 patients with newly diagnosed mild to moderate EH were enrolled in the present study. Four ACE 2 tag SNPs (rs2074192, rs4646171, rs4646155 and rs2106809) were genotyped, and major haplotypes consisting of these 4 SNP s were reconstructed for all subjects. Circulating levels of ACE 2, angiotensin‐(1‐7) and angiotensin‐(1‐9) were measured using enzyme‐linked immunosorbent assay. Results In female subjects, linear regression analysis suggested that rare alleles of ACE 2 rs2074192 and rs2106809 were associated with reduced circulating angiotensin‐(1‐7) levels ( P =.007 and P =.006, respectively). ACE 2 haplotype CAGC was associated with elevated circulating angiotensin‐(1‐7) levels ( P =.03) whereas TAGT was associated with reduced circulating angiotensin‐(1‐7) levels in females ( P .001). Univariate linear regression analysis revealed that circulating ACE 2 levels were positively associated with systolic blood pressure ( P =.02), mean arterial pressure ( P =.02) and serum creatinine ( P .001) in females whereas circulating ACE 2 levels were positively associated with age ( P .001) and serum creatinine ( P .001) in males. What is new and conclusion ACE 2 SNP s and haplotypes are associated with circulating angiotensin‐(1‐7) levels. ACE 2 genetic variants may be the determinants of circulating angiotensin‐(1‐7) levels in hypertensive females.