4G/4G genotype of PAI-1 gene is associated with reduced risk of stroke in elderly.

Abstract

BACKGROUND AND PURPOSE:

Plasminogen activator inhibitor type 1 (PAI-1) is the main inhibitor of fibrinolysis, and high levels may increase the risk of cardiovascular disease. The 4G/5G polymorphism affects PAI-1 gene transcription with lower levels of plasma PAI-1 in the presence of the 5G allele. We investigated whether plasma PAI-1 and 4G/5G genotype would predict the occurrence of cardiovascular events at old age.

METHODS:

Relative risks for cardiovascular events and all-cause mortality were obtained in strata of PAI-1 activity and 4G/5G genotype in a population-based study of 637 Dutch elderly with 7.8 years of follow-up.

RESULTS:

The 4G/4G genotype was associated with a decreased risk of stroke (relative risk [RR]=0.4; 95% CI, 0.2 to 0.9), transient ischemic attack (RR=0.3; 95% CI, 0.1 to 0.8), and cardiovascular mortality (RR=0.5; 95% CI, 0.3 to 1.0) after adjustment for age, sex, and time of blood sampling. 4G carriers had an increased risk of myocardial infarction, but this was not statistically significant. Subjects with high plasma PAI-1 activity were at increased risk of stroke (RR=3.3 in highest versus lowest tertile; 95% CI, 1.5 to 7.1), cardiovascular mortality (RR=2.3; 95% CI, 1.2 to 4.4), and all-cause mortality (RR=1.5; 95% CI, 1.1 to 2.1).

CONCLUSIONS:

Our results provide support for a protective effect of the 4G allele against stroke, which is notable given the direct relationship between stroke and PAI-1 activity. We hypothesize that a local increase in tissue PAI-1 associated with the 4G allele may stabilize plaques, thereby reducing the risk of cerebrovascular disease.

• Authors: Tiny Hoekstra, Johanna M Geleijnse, Cornelis Kluft, Erik J Giltay, Frans J Kok, Evert G Schouten
• Journal: Stroke (Stroke) Vol. 34 Issue 12 Pg. 2822-8 (Dec 2003) ISSN: 1524-4628 [Electronic] United States
• PMID: 14605330 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Plasminogen Activator Inhibitor 1

Topics

• Aged
• Aged, 80 and over
• Cardiovascular Diseases (epidemiology, genetics, mortality)
• Cohort Studies
• Disease-Free Survival
• Female
• Genotype
• Humans
• Incidence
• Male
• Netherlands (epidemiology)
• Plasminogen Activator Inhibitor 1 (blood, genetics)
• Polymorphism, Genetic (genetics)
• Risk
• Risk Assessment
• Stroke (epidemiology, genetics, mortality)