Relationship between genetic variants of ACE2 gene and circulating levels of ACE2 and its metabolites

• Published in: Journal of clinical pharmacy and therapeutics Vol. 43; no. 2; pp. 189 - 195
• Main Authors: Chen, Y. Y., Zhang, P., Zhou, X. M., Liu, D., Zhong, J. C., Zhang, C. J., Jin, L. J., Yu, H. M.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2018
• Subjects: ACE2; ACE2 gene; Aged; Alleles; Angiotensin; Angiotensin I - blood; Angiotensin-Converting Enzyme 2; angiotensin‐(1‐7); Blood pressure; Blood Pressure - genetics; Creatinine; Enzymes; Essential Hypertension - blood; Essential Hypertension - genetics; Essential Hypertension - metabolism; Female; Females; Gene Frequency - genetics; Genetic diversity; Genetic factors; Genotype; haplotype; Haplotypes; Health risk assessment; Heritability; Humans; Male; Metabolites; Middle Aged; Peptide Fragments - blood; Peptidyl-Dipeptidase A - blood; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Polymorphism, Single Nucleotide - genetics; Regression analysis; single nucleotide polymorphisms; Single-nucleotide polymorphism; angiotensin-(1-7); angiotensin-converting enzyme 2; haplotype; single nucleotide polymorphisms
• ISSN: 0269-4727; 1365-2710; 1365-2710
• DOI: 10.1111/jcpt.12625

Summary What is known Angiotensin‐converting enzyme 2 (ACE2) plays an important role in the development of essential hypertension (EH). Genetic factors remarkably influence circulating ACE2 level. Objective Because heritability had remarkable effects on circulating ACE2, we designed this study to shed light on whether circulating levels of ACE2, angiotensin‐(1‐7) and angiotensin‐(1‐9) were linked to single nucleotide polymorphisms (SNPs) and haplotypes in ACE2 gene. Methods A total of 213 patients with newly diagnosed mild to moderate EH were enrolled in the present study. Four ACE2 tag SNPs (rs2074192, rs4646171, rs4646155 and rs2106809) were genotyped, and major haplotypes consisting of these 4 SNPs were reconstructed for all subjects. Circulating levels of ACE2, 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 ACE2 rs2074192 and rs2106809 were associated with reduced circulating angiotensin‐(1‐7) levels (P=.007 and P=.006, respectively). ACE2 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 ACE2 levels were positively associated with systolic blood pressure (P=.02), mean arterial pressure (P=.02) and serum creatinine (P<.001) in females whereas circulating ACE2 levels were positively associated with age (P<.001) and serum creatinine (P<.001) in males. What is new and conclusion ACE2 SNPs and haplotypes are associated with circulating angiotensin‐(1‐7) levels. ACE2 genetic variants may be the determinants of circulating angiotensin‐(1‐7) levels in hypertensive females. Relationship between genetic variants of ACE2 gene and circulating levels of ACE2 and its metabolites were studied in patients with EH. EH, essential hypertension; ACE2, angiotensin converting enzyme 2; Ang‐ (1–7), angiotensin‐ (1–7); Ang‐ (1–9), angiotensin‐ (1–9); ELISA, enzyme‐ linked immunosorbent assay.