Hypertension and hypertensive left ventricular hypertrophy are associated with ACE2 genetic polymorphism

Aims: Renin-angiotensin system modulates cardiac structure independent of blood pressure. The present study aimed at investigating whether single nucleotide polymorphism (SNP) and haplotype of angiotensin converting enzyme 2 (ACE2) could influence blood pressure and the susceptibility to hypertensive left ventricular hypertrophy (LVH). Subjects and methods: A total of 647 patients (347 females and 300 males) with newly diagnosed mild to moderate essential hypertension were enrolled in a blood pressure matched, case-control study. Four ACE2 tagSNPs (rs2074192, rs4646176, rs4646155 and rs2106809) were genotyped and major haplotypes consisting of these four SNPs were reconstructed for all subjects. Key findings: In females, minor alleles of ACE2 rs2074192 and rs2106809 respectively conferred a 2.1 and 2.0 fold risk for LVH. ACE2 haplotype TCGT increased the risk for LVH while another haplotype CCGC decreased the risk in females. The covariates-adjusted mean left ventricular mass index was 11% greater in TCGT haplotype carriers than in noncarriers in women. In females, the covariates-adjusted mean systolic blood pressure was 3.4 mm Hg lower in CCGC haplotype carriers than in noncarriers. In males, the covariates-adjusted mean systolic blood pressure was 2.4 mm Hg lower in CCGC haplotype carriers than in noncarriers. Significance: ACE2 tagSNPs rs2074192 and rs2106809 as well as major haplotypes CCGC and TCGT may serve as novel risk markers for LVH in hypertensive patients.