Elsevier

American Heart Journal

Volume 152, Issue 6, December 2006, Pages 1109-1115
American Heart Journal

Clinical Investigation
Genetics
Plasminogen activator inhibitor type 1 gene polymorphisms and haplotypes are associated with plasma plasminogen activator inhibitor type 1 levels but not with myocardial infarction or stroke

https://doi.org/10.1016/j.ahj.2006.06.021Get rights and content

Background

The 4G allele in the promoter region of the plasminogen activator inhibitor type 1 (PAI-1) gene is associated with higher plasma PAI-1 levels and activity, but its association with cardiovascular diseases is unclear. We investigated the association of polymorphisms and common haplotypes of the PAI-1 gene with plasma PAI-1 levels, as well as the risk of myocardial infarction and stroke.

Methods and Results

This study is a prospective analysis of 2995 community-based participants (41% blacks and 51% women) aged 70 to 79 years old in the Health, Aging, and Body Composition Study. From 1997/1998 to 2001, 177 myocardial infarction events and 101 stroke events were identified. In addition to the 4G/5G polymorphism, 2 potential functional variants and other 4 haplotype-tagging variants were genotyped. In general linear models, the 4G allele was associated with higher PAI-1 levels after adjusting for age, sex, race, and site (26, 29, and 32 ng/mL for 5G/5G, 4G/5G, and 4G/4G, respectively; P for trend < .0001), but none of the other 6 polymorphisms was associated with PAI-1 levels. Haplotype analysis produced similar results. However, in Cox proportional hazard models, neither the polymorphisms nor the common haplotypes of the PAI-1 gene was associated with the risk of either myocardial infarction or stroke.

Conclusions

The 4G allele is associated with higher PAI-1 levels, but this study does not support an association of the PAI gene polymorphisms with the risk of either myocardial infarction or stroke.

Section snippets

Methods

The Health, Aging, and Body Composition (Health ABC) Study is a prospective, community-based study designed to investigate the effects of body composition on morbidity, functional limitations, and mortality. A total of 3075 participants were recruited from a random sample of white and all black Medicare beneficiaries residing within each zip code from the metropolitan areas surrounding Pittsburgh and Memphis from 1997 to 1998. Participants were eligible if they were 70 to 79 years of age;

Results

At baseline, the participants who developed myocardial infarction during the follow-up were more likely to be male, smokers and prevalent cases of coronary heart disease, stroke, and diabetes, reported less participation of physical activity, and had lower HDL cholesterol levels than those who did not develop myocardial infarction (Table I). In whites, those who developed myocardial infarction also had higher plasma PAI-1 levels. The participants who developed stroke were more likely to be

Discussion

This study, to our knowledge, is the first study on the association of common PAI-1 gene haplotypes with myocardial infarction and stroke. The common haplotypes containing the 4G allele were associated with higher PAI-1 levels overall and in whites. The pattern was similar in blacks, although the association was not statistically significant. However, neither PAI-1 gene polymorphisms nor common haplotypes were associated with the risk of either myocardial infarction or stroke.

In accordance with

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    Support for this study was given by the Laboratory of Epidemiology, Demography and Biometry of the National Institute on Aging under National Institutes of Health's contract numbers N01-AG-6-2106, N01-AG-6-2102, and N01-AG-6-2103, and the Wake Forest University Claude D. Pepper Older Americans Independence Center (NIH P30-AG21332). In addition, Hologic Inc supported a validation study on body composition, but the investigators retained full independence in the conduct of this research.

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