Lack of association of a common polymorphism of the plasminogen activator inhibitor-1 gene with coronary artery disease and myocardial infarction.
OBJECTIVE
The study was done to assess whether the common polymorphic allele (4G) of the plasminogen activator inhibitor-1 (PAI-1) gene is associated with coronary artery disease (CAD) or myocardial infarction (MI).


BACKGROUND
Impaired fibrinolytic function has been associated with CAD and MI. Plasminogen activator inhibitor-1 plays a central role in intravascular thrombosis and thrombolysis; the common insertion/deletion polymorphism (4G/5G) of PAI-1 has been correlated with altered PAI-1 levels and proposed as a coronary risk factor.


METHODS
Blood was drawn and DNA extracted from 1,353 consenting patients undergoing coronary angiography. The 4G and 5G alleles of PAI-1 were amplified using specific primers. Amplified products were visualized by staining with ethidium bromide after electrophoresis in 1.5% agarose.


RESULTS
Patient age averaged 63.5 (SD 11.7) years; 70% were men, 28% had a history of MI, 66% had severe CAD (>60% stenosis), and 23% had no CAD or MI. Overall, the frequency of the 4G allele was 54.2%, and 78% of patients were 4G carriers. Genotypic distributions were: 4G/4G = 30.1%, 4G/5G = 47.9%, and 5G/5G = 21.8%. Neither carriage of 4G (CAD odds ratio [OR] = 1.08 [0.80 to 1.46], MI OR = 1.11 [0.83 to 1.49]) nor 4G/4G homozygosity (CAD OR = 1.07, MI OR = 0.98) was associated with CAD or MI. In multivariate analyses, risk factors associated with CAD were (in order): gender, age, smoking, diabetes, cholesterol, and hypertension; for MI, they were gender, smoking, and cholesterol.


CONCLUSIONS
A common PAI-1 polymorphism (4G) was not importantly associated with angiographic CAD or history of MI in a Caucasian population. Modest risk (i.e., OR <1.5), especially for MI, or risk in association with other factors, cannot be excluded.
Anderson
J L
JL
Department of Medicine, University of Utah School of Medicine, Salt Lake City 84132, USA.
Muhlestein
J B
JB
Habashi
J
J
Carlquist
J F
JF
Bair
T L
TL
Elmer
S P
SP
Davis
B P
BP
D000368:Aged; D000483:Alleles; D003327:Coronary Disease / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors
D017395:Plasminogen Activator Inhibitor 1; D004247:DNA