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 language | English |
|---|---|
| Pages (from-to) | 191-195 |
| Number of pages | 5 |
| Journal | Cerebrovascular Diseases |
| Volume | 22 |
| Issue number | 2-3 |
| DOIs | |
| Publication status | Published - Jul 2006 |
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Keywords
- Cerebral ischemia
- Cholesterol
- Plasminogen activator inhibitor-1 polymorphism
- Triglycerides
ASJC Scopus subject areas
- Clinical Neurology
Cite this
An effect of the PAI-1 4G/5G polymorphism on cholesterol levels may explain conflicting associations with myocardial infarction and stroke. / Boncoraglio, Giorgio B.; Bodini, Antonella; Brambilla, Carla; Carriero, Maria Rita; Ciusani, Emilio; Parati, Eugenio A.
In: Cerebrovascular Diseases, Vol. 22, No. 2-3, 07.2006, p. 191-195.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=33746348915&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33746348915&partnerID=8YFLogxK
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
ER -