Gene polymorphisms of angiotensin-converting enzyme and angiotensinogen and risk of idiopathic ischemic stroke

Gene. 2019 Mar 10:688:163-170. doi: 10.1016/j.gene.2018.11.080. Epub 2018 Dec 4.

Abstract

Objective: The renin-angiotensin system (RAS) is a hormonal signaling mechanism implicated in the atherosclerosis and regulation of blood pressure. Angiotensin-converting enzyme (ACE) a key enzyme in the RAS, plays important roles in vascular remodeling atherosclerosis, and ischemic stroke. The aim of this study was to examine the possible contribution of the I/D in the ACE gene, M235T and T174M in the angiotensinogen (AGT) gene polymorphisms with ischemic stroke in young Mexican population.

Materials and methods: A total of 224 patients with diagnosis of idiopathic ischemic stroke ≤45 years of age, and 224 controls matched by age and gender, were recruited from 2006 and 2016. The I/D, M235T and T174M polymorphisms were determined in all participants by PCR-RFLP.

Results: There was a significant difference in the M235T genotype distribution (p = 0.01) and allele frequency between two groups (p = 0.01). Also, we found a significant difference in the T174M genotype distribution (p = 0.01) and the allele frequency between groups; (p = 0.02). In contrast, in I/D polymorphism, there was a similar genotype distribution; (p = 0.20) and allele distribution (p = 0.20). There were independent factors for ischemic stroke: M235T and T174M polymorphisms, smoking, hypertension, and familial history of atherothrombotic disease. The AGT levels were increased in the group of patients with stroke compared with the control group, but the AGT levels were not influenced by the allele or genotype in each polymorphism.

Conclusions: The M235T and T174M polymorphisms represented an increased risk for stroke in young Mexican individuals. In contrast, the I/D was not associated with in the same group of patients. The AGT levels were higher in the acute phase of stroke, but it was not determined by the polymorphisms.

Keywords: Genetic risk; I/D; Idiopathic ischemic stroke; M235T; T174M.

MeSH terms

  • Adult
  • Alleles
  • Angiotensinogen / genetics*
  • Blood Pressure / genetics
  • Brain Ischemia / genetics*
  • Case-Control Studies
  • Female
  • Gene Frequency / genetics
  • Genotype
  • Humans
  • Hypertension / genetics
  • Male
  • Mexico
  • Peptidyl-Dipeptidase A / genetics*
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Restriction Fragment Length / genetics
  • Renin-Angiotensin System / genetics
  • Risk Factors
  • Stroke / genetics*

Substances

  • AGT protein, human
  • Angiotensinogen
  • ACE protein, human
  • Peptidyl-Dipeptidase A