An effect of the PAI-1 4G/5G polymorphism on cholesterol levels may explain conflicting associations with myocardial infarction and stroke

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Abstract

Background and Purpose: The gene-encoding plasminogen activator inhibitor type 1 (PAI-1) has a common 4G/5G 'functional' polymorphism, and people homozygous for the 4G allele have higher PAI-1 plasma concentrations. The 4G/4G genotype is associated with increased risk of myocardial infarction but paradoxically protects against stroke. We hypothesized that this paradox may be explained via an effect of the PAI-1 polymorphism on plasma lipids. Methods: We studied 71 consecutive Italian patients referred to our Institute for first stroke or vascular cognitive impairment. PAI-1 gene 4G/5G polymorphism, total plasma cholesterol, plasma triglycerides, sex, age, smoking, oral contraceptive use, statin therapy, hypertension, diabetes, and history of myocardial infarction were examined. Results: The 4G/4G genotype was significantly associated with high cholesterol (p = 0.003) but not with triglycerides (p = 0.39). Adjusted odds ratios were: 5.8 for 4G/4G vs. 4G/5G (95% CI, 3.1-23.0), and 15.9 for 4G/4G vs. 5G/5G (95% CI, 2.4-105.0). Conclusions: This finding may explain the involvement of the PAI-1 polymorphism in the clustering of atherothrombotic risk factors, and why people with the 4G/4G genotype are at increased risk for myocardial infarction. Stroke is not so clearly related to hypercholesterolemia and other effects of the 4G/4G genotype (perhaps increased PAI-1 expression) may protect against stroke.

Original languageEnglish
Pages (from-to)191-195
Number of pages5
JournalCerebrovascular Diseases
Volume22
Issue number2-3
DOIs
Publication statusPublished - Jul 2006

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Plasminogen Activator Inhibitor 1
Stroke
Myocardial Infarction
Cholesterol
Genotype
Triglycerides
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Oral Contraceptives
Hypercholesterolemia
Genes
Blood Vessels
Cluster Analysis
Smoking
Alleles
Odds Ratio
Hypertension
Lipids

Keywords

  • Cerebral ischemia
  • Cholesterol
  • Plasminogen activator inhibitor-1 polymorphism
  • Triglycerides

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

@article{559dfe67b5b7424abf0c1a76dc26cd85,
title = "An effect of the PAI-1 4G/5G polymorphism on cholesterol levels may explain conflicting associations with myocardial infarction and stroke",
abstract = "Background and Purpose: The gene-encoding plasminogen activator inhibitor type 1 (PAI-1) has a common 4G/5G 'functional' polymorphism, and people homozygous for the 4G allele have higher PAI-1 plasma concentrations. The 4G/4G genotype is associated with increased risk of myocardial infarction but paradoxically protects against stroke. We hypothesized that this paradox may be explained via an effect of the PAI-1 polymorphism on plasma lipids. Methods: We studied 71 consecutive Italian patients referred to our Institute for first stroke or vascular cognitive impairment. PAI-1 gene 4G/5G polymorphism, total plasma cholesterol, plasma triglycerides, sex, age, smoking, oral contraceptive use, statin therapy, hypertension, diabetes, and history of myocardial infarction were examined. Results: The 4G/4G genotype was significantly associated with high cholesterol (p = 0.003) but not with triglycerides (p = 0.39). Adjusted odds ratios were: 5.8 for 4G/4G vs. 4G/5G (95{\%} CI, 3.1-23.0), and 15.9 for 4G/4G vs. 5G/5G (95{\%} CI, 2.4-105.0). Conclusions: This finding may explain the involvement of the PAI-1 polymorphism in the clustering of atherothrombotic risk factors, and why people with the 4G/4G genotype are at increased risk for myocardial infarction. Stroke is not so clearly related to hypercholesterolemia and other effects of the 4G/4G genotype (perhaps increased PAI-1 expression) may protect against stroke.",
keywords = "Cerebral ischemia, Cholesterol, Plasminogen activator inhibitor-1 polymorphism, Triglycerides",
author = "Boncoraglio, {Giorgio B.} and Antonella Bodini and Carla Brambilla and Carriero, {Maria Rita} and Emilio Ciusani and Parati, {Eugenio A.}",
year = "2006",
month = "7",
doi = "10.1159/000093604",
language = "English",
volume = "22",
pages = "191--195",
journal = "Cerebrovascular Diseases",
issn = "1015-9770",
publisher = "S. Karger AG",
number = "2-3",

}

TY - JOUR

T1 - An effect of the PAI-1 4G/5G polymorphism on cholesterol levels may explain conflicting associations with myocardial infarction and stroke

AU - Boncoraglio, Giorgio B.

AU - Bodini, Antonella

AU - Brambilla, Carla

AU - Carriero, Maria Rita

AU - Ciusani, Emilio

AU - Parati, Eugenio A.

PY - 2006/7

Y1 - 2006/7

N2 - Background and Purpose: The gene-encoding plasminogen activator inhibitor type 1 (PAI-1) has a common 4G/5G 'functional' polymorphism, and people homozygous for the 4G allele have higher PAI-1 plasma concentrations. The 4G/4G genotype is associated with increased risk of myocardial infarction but paradoxically protects against stroke. We hypothesized that this paradox may be explained via an effect of the PAI-1 polymorphism on plasma lipids. Methods: We studied 71 consecutive Italian patients referred to our Institute for first stroke or vascular cognitive impairment. PAI-1 gene 4G/5G polymorphism, total plasma cholesterol, plasma triglycerides, sex, age, smoking, oral contraceptive use, statin therapy, hypertension, diabetes, and history of myocardial infarction were examined. Results: The 4G/4G genotype was significantly associated with high cholesterol (p = 0.003) but not with triglycerides (p = 0.39). Adjusted odds ratios were: 5.8 for 4G/4G vs. 4G/5G (95% CI, 3.1-23.0), and 15.9 for 4G/4G vs. 5G/5G (95% CI, 2.4-105.0). Conclusions: This finding may explain the involvement of the PAI-1 polymorphism in the clustering of atherothrombotic risk factors, and why people with the 4G/4G genotype are at increased risk for myocardial infarction. Stroke is not so clearly related to hypercholesterolemia and other effects of the 4G/4G genotype (perhaps increased PAI-1 expression) may protect against stroke.

AB - Background and Purpose: The gene-encoding plasminogen activator inhibitor type 1 (PAI-1) has a common 4G/5G 'functional' polymorphism, and people homozygous for the 4G allele have higher PAI-1 plasma concentrations. The 4G/4G genotype is associated with increased risk of myocardial infarction but paradoxically protects against stroke. We hypothesized that this paradox may be explained via an effect of the PAI-1 polymorphism on plasma lipids. Methods: We studied 71 consecutive Italian patients referred to our Institute for first stroke or vascular cognitive impairment. PAI-1 gene 4G/5G polymorphism, total plasma cholesterol, plasma triglycerides, sex, age, smoking, oral contraceptive use, statin therapy, hypertension, diabetes, and history of myocardial infarction were examined. Results: The 4G/4G genotype was significantly associated with high cholesterol (p = 0.003) but not with triglycerides (p = 0.39). Adjusted odds ratios were: 5.8 for 4G/4G vs. 4G/5G (95% CI, 3.1-23.0), and 15.9 for 4G/4G vs. 5G/5G (95% CI, 2.4-105.0). Conclusions: This finding may explain the involvement of the PAI-1 polymorphism in the clustering of atherothrombotic risk factors, and why people with the 4G/4G genotype are at increased risk for myocardial infarction. Stroke is not so clearly related to hypercholesterolemia and other effects of the 4G/4G genotype (perhaps increased PAI-1 expression) may protect against stroke.

KW - Cerebral ischemia

KW - Cholesterol

KW - Plasminogen activator inhibitor-1 polymorphism

KW - Triglycerides

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U2 - 10.1159/000093604

DO - 10.1159/000093604

M3 - Article

C2 - 16735791

AN - SCOPUS:33746348915

VL - 22

SP - 191

EP - 195

JO - Cerebrovascular Diseases

JF - Cerebrovascular Diseases

SN - 1015-9770

IS - 2-3

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