Association between renin-angiotensin-aldosterone system genotypes and haplotypes and risk of ischemic stroke of atherosclerotic etiology

Acta Neurol Scand. 2009 Jun;119(6):356-63. doi: 10.1111/j.1600-0404.2008.01105.x.

Abstract

Objective: The association of renin C-4063T and angiotensinogen (AGT) T174M, AGT M235T and AGT A-6G polymorphisms with ischemic stroke of atherosclerotic etiology was investigated in 329 Tunisian patients with stroke and 444 controls.

Materials and methods: Genotyping was performed using PCR-RFLP and the contributions of polymorphisms to the risk of stroke were analyzed using haplotype and multivariate regression analysis.

Results: AGT 235T and AGT-6G allele and AGT 235T/T, AGT-6A/G and AGT-6G/G genotype frequencies were higher in patients. Linkage disequilibrium (LD) was noted for AGT174T with AGT235M and AGT(-6)A in patients, while AGT235M was in LD with AGT(-6)A in controls and AGT235T was in LD with AGT(-6)G in both groups. The AGT 174T/235T/-6A and AGT 174T/235M/-6G haplotypes were positively and negatively associated with stroke respectively. Multivariate regression analysis identified AGT 174T/235M/-6A, AGT 174T/235T/-6G, AGT 174T/235T/-6A and AGT 174M/235T/-6A haplotypes to be significantly associated with an increased risk of stroke.

Conclusions: Renin-angiotensin-aldosterone system polymorphisms influence the risk of atherosclerotic stroke in Tunisians.

MeSH terms

  • Angiotensinogen / genetics*
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Haplotypes
  • Humans
  • Intracranial Arteriosclerosis / complications
  • Intracranial Arteriosclerosis / genetics*
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Renin / genetics*
  • Renin-Angiotensin System / genetics
  • Risk Factors
  • Stroke / etiology
  • Stroke / genetics*
  • Tunisia

Substances

  • Angiotensinogen
  • Renin