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

Life Sci. 2019 May 15:225:39-45. doi: 10.1016/j.lfs.2019.03.059. Epub 2019 Mar 24.

Abstract

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.

Keywords: Angiotensin converting enzyme 2; Haplotype; Left ventricular hypertrophy; Renin-angiotensin system; Single nucleotide polymorphism.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Angiotensin-Converting Enzyme 2
  • Case-Control Studies
  • Female
  • Genetic Markers*
  • Genotype
  • Humans
  • Hypertension / genetics*
  • Hypertension / pathology
  • Hypertrophy, Left Ventricular / genetics*
  • Hypertrophy, Left Ventricular / pathology
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Single Nucleotide*
  • Young Adult

Substances

  • Genetic Markers
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2