Analysis of the Association Between Polymorphisms within PAI-1 and ACE genes and Ischemic Stroke Outcome After rt-PA Therapy

J Pharm Pharm Sci. 2019;22(1):142-149. doi: 10.18433/jpps30339.

Abstract

Purpose: Treatment of Ischemic stroke (IS) in acute phase is based on the use of thrombolytic rt-PA therapy. We aimed to determine whether different alleles and genotypes of I/D ACE gene and 4G/5G PAI-1 gene polymorphisms may influence outcome of rt-PA therapy in patients with IS and the occurrence of haemorrhagic transformation (HT).

Methods: Our study included 94 consecutive patients with IS treated with rt-PA. Modified Rankin Scale (mRS) at 3rd month after IS was used to determine the stroke outcome, with scores 0-1 defining the favourable outcome, and scores 2-6 defining poor outcome. Genotypisation of the ACE-1 I/D polymorphism was performed by polymerase chain reaction and of the PAI-1 4G/5G polymorphism by polymerase chain reaction - restriction fragment length analysis.

Results: Regarding PAI-I 4G/5G polymorphism, 44 patients (46.8%) were heterozygotes, and the number of 4G/4G and 5G/5G homozygotes was the same - 25 each (26.6%). Number of heterozygotes for the ACE I/D polymorphism was 54 (57.4%), 9 patients (9.6%) had II, and 31 (33%) DD genotypes. A favourable outcome was recorded in 26 (28.0%) and the poor outcome in 67 (72.0%) patients. Favourable and poor outcome groups did not differ significantly in PAI-1 4G/5G and ACE I/D polymorphisms genotype or allele frequencies. There was a statistically significant difference in the occurrence of HT between patients with ACE II and patients with ACE ID or DD genotypes (p=0.035).

Conclusion: Results of our study suggest that stroke patients with ACE II genotype, treated with rt-PA, may be at risk of HT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / genetics
  • Female
  • Fibrinolytic Agents / therapeutic use*
  • Genotype
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Peptidyl-Dipeptidase A / genetics*
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Polymorphism, Genetic
  • Stroke / drug therapy*
  • Stroke / genetics
  • Tissue Plasminogen Activator / therapeutic use*
  • Treatment Outcome
  • Young Adult

Substances

  • Fibrinolytic Agents
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • ACE protein, human
  • Peptidyl-Dipeptidase A
  • Tissue Plasminogen Activator