Chen Y Y, Zhang P, Zhou X M, Liu D, Zhong J C, Zhang C J, Jin L J, Yu H M
Department of Cardiology, Shantou Central Hospital and Affiliated Shantou Hospital of Sun Yat-sen University, Shantou, China.
Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
J Clin Pharm Ther. 2018 Apr;43(2):189-195. doi: 10.1111/jcpt.12625. Epub 2017 Sep 11.
Angiotensin-converting enzyme 2 (ACE2) plays an important role in the development of essential hypertension (EH). Genetic factors remarkably influence circulating ACE2 level.
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.
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.
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.
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.
血管紧张素转换酶2（ACE2）在原发性高血压（EH）的发生发展中起重要作用。遗传因素对循环中ACE2水平有显著影响。
由于遗传力对循环中ACE2有显著影响，我们设计了本研究，以阐明ACE2、血管紧张素-（1-7）和血管紧张素-（1-9）的循环水平是否与ACE2基因中的单核苷酸多态性（SNP）和单倍型相关。
本研究共纳入213例新诊断的轻度至中度EH患者。对4个ACE2标签SNP（rs2074192、rs4646171、rs4646155和rs2106809）进行基因分型，并为所有受试者重建由这4个SNP组成的主要单倍型。采用酶联免疫吸附测定法测量ACE2、血管紧张素-（1-7）和血管紧张素-（1-9）的循环水平。
在女性受试者中，线性回归分析表明，ACE2 rs2074192和rs2106809的罕见等位基因与循环中血管紧张素-（1-7）水平降低相关（分别为P = 0.007和P = 0.006）。ACE2单倍型CAGC与循环中血管紧张素-（1-7）水平升高相关（P = 0.03），而TAGT与女性循环中血管紧张素-（1-7）水平降低相关（P < 0.001）。单变量线性回归分析显示，女性循环中ACE2水平与收缩压（P = 0.02）、平均动脉压（P = 0.02）和血清肌酐（P < 0.001）呈正相关，而男性循环中ACE2水平与年龄（P < 0.001）和血清肌酐（P < 0.001）呈正相关。
ACE2 SNP和单倍型与循环中血管紧张素-（1-7）水平相关。ACE2基因变异可能是高血压女性循环中血管紧张素-（1-7）水平的决定因素。
