Jl. Anderson et al., Lack of association of a common polymorphism of the plasminogen activator inhibitor-1 gene with coronary artery disease and myocardial infarction, J AM COL C, 34(6), 1999, pp. 1778-1783
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
OBJECTIVES The study was done to assess whether the common polymorphic alle
le (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 pla;vs a central role in intravascula
r 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 un
dergoing coronary angiography. The 4G and 5G alleles of PAI-1 were amplifie
d using specific primers. Amplified products were visualized by staining wi
th ethidium bromide after electrophoresis in 1.5% ag-arose.
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 M
I. Overall, the frequency of the 4G allele was 54.2%, and 78% of patients w
ere 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, d
iabetes, cholesterol, and hypertension; for MI, they were gender, smoking,
CONCLUSIONS A common PAI-1 polymorphism (4G) was not importantly associated
with angiographic CAD or history of MI in a Caucasian population. Modest r
isk (i.e., OR <1.5), especially for MI, or risk in association with other f
actors, cannot be excluded (C) 1999 by the American College of Cardiology.