CLINICAL STUDIES
Lack of association of a common polymorphism of the plasminogen activator inhibitor-1 gene with coronary artery disease and myocardial infarction
Jeffrey L. Anderson, MD, FACC*,
Joseph B. Muhlestein, MD, FACC*  ,
Jessica Habashi, BS* ,
John F. Carlquist, PhD* ,
Tami L. Bair, BS* ,
Sidney P. Elmer, BS* and
Brent P. Davis, BS*
* Department of Medicine, Division of Cardiology, University of Utah School of Medicine, Salt Lake City, Utah, USA
LDS Hospital, Salt Lake City, Utah, USA
Manuscript received December 29, 1998;
revised manuscript received May 4, 1999,
accepted August 12, 1999.
Reprint requests and correspondence: Dr. Jeffrey L. Anderson, Division of Cardiology, University of Utah School of Medicine, 50 North Medical Drive, Salt Lake City, Utah 84132
OBJECTIVES
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.
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Abbreviations and Acronyms
| | ACS | = acute coronary syndrome | | bp | = base pair | | CAD | = coronary artery disease | | DNA | = deoxyribonucleic acid | | EDTA | = ethylenediaminetetraacetic acid | | MI | = myocardial infarction | | OR | = odds ratio | | PAI | = plasminogen activator inhibitor | | PCR | = polymerase chain reaction | | VLDL | = very low density lipoprotein |
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