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

Jingzhong Ding, Barbara J. Nicklas, Daniele Daniele Fallin, Nathalie de Rekeneire, Stephen B. Kritchevsky, Marco Pahor, Nicolas Rodondi, Rongling Li, Joseph M. Zmuda, Tamara B. Harris

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1109-1115
Number of pages7
JournalAmerican Heart Journal
Volume152
Issue number6
DOIs
StatePublished - Dec 2006

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Plasminogen Activator Inhibitor 1
Haplotypes
Stroke
Myocardial Infarction
Genes
Alleles
Body Composition
Proportional Hazards Models
Genetic Promoter Regions
Linear Models
Cardiovascular Diseases
Health

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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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. / Ding, Jingzhong; Nicklas, Barbara J.; Fallin, Daniele Daniele; de Rekeneire, Nathalie; Kritchevsky, Stephen B.; Pahor, Marco; Rodondi, Nicolas; Li, Rongling; Zmuda, Joseph M.; Harris, Tamara B.

In: American Heart Journal, Vol. 152, No. 6, 12.2006, p. 1109-1115.

Research output: Contribution to journalArticle

Ding, Jingzhong ; Nicklas, Barbara J. ; Fallin, Daniele Daniele ; de Rekeneire, Nathalie ; Kritchevsky, Stephen B. ; Pahor, Marco ; Rodondi, Nicolas ; Li, Rongling ; Zmuda, Joseph M. ; Harris, Tamara B. / 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. In: American Heart Journal. 2006 ; Vol. 152, No. 6. pp. 1109-1115.
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abstract = "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.",
author = "Jingzhong Ding and Nicklas, {Barbara J.} and Fallin, {Daniele Daniele} and {de Rekeneire}, Nathalie and Kritchevsky, {Stephen B.} and Marco Pahor and Nicolas Rodondi and Rongling Li and Zmuda, {Joseph M.} and Harris, {Tamara B.}",
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T1 - 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

AU - Ding, Jingzhong

AU - Nicklas, Barbara J.

AU - Fallin, Daniele Daniele

AU - de Rekeneire, Nathalie

AU - Kritchevsky, Stephen B.

AU - Pahor, Marco

AU - Rodondi, Nicolas

AU - Li, Rongling

AU - Zmuda, Joseph M.

AU - Harris, Tamara B.

PY - 2006/12

Y1 - 2006/12

N2 - 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.

AB - 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.

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DO - 10.1016/j.ahj.2006.06.021

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SP - 1109

EP - 1115

JO - American Heart Journal

JF - American Heart Journal

SN - 0002-8703

IS - 6

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