Prediction of the risk of myocardial infarction from polymorphisms in candidate genes - Prediction of the risk of myocardial infarction from polymorphisms in candidate genes


The goal of this study was to assess the ability of genetic polymorphism in candidate genes to predict subsequent risk of acute MI (AMI).

Study Design

Study Design:

Drug/Procedures Used:

A fluorescence or colorimetry-based allele-specific DNA-primer – probe assay system was used to determine the genotypes of 112 polymorphisms of 71 candidate genes in unrelated Japanese patients with myocardial infarction (n=2,819) as well as in unrelated Japanese controls (n=2,242) seen at one of the 15 participating hospitals between July 1994 and December 2001. The candidate genes, that have been previously shown to be associated with coronary atherosclerosis or spasm or the risk factors for coronary artery disease, were selected using public databases.

Principal Findings:

Based on preliminary screening of the 112 polymorphisms for an association with myocardial infarction in 909 subjects selected randomly, 19 polymorphisms were selected in men and 18 in women by means of logistic regression analysis, after adjustment for age, body-mass index, and the prevalence of smoking, hypertension, diabetes mellitus, hypercholesterolemia, and hyperuricemia. The selected polymorphisms when evaluated in the remaining 4152 subjects using similar logistic regression analysis revealed that the risk of myocardial infarction was significantly associated with the C1019T polymorphism in the connexin 37 gene (Odds ratio [OR] 1.4 95% confidence interval [CI] 1.1-1.6; p<0.001)in men and the 4G-668/5G polymorphism in the plasminogen-activator inhibitor type 1 gene (OR 1.6, 95% CI 1.2-2.1; p<0.001) and the 5A-1171/6A polymorphism in the stromelysin-1 gene (OR 4.7, 95% CI 2.0-12.2; p<0.001)in women.


Among patients at risk of myocardial infarction, the determination of the connexin type 37, plasminogen-activator inhibitor type 1, and stromelysin-1 genotypes may aid in the identification of patients at risk for subsequent MI and by extension may aid in the identification of patients who might benefit from aggressive preventive measures. This intriguing study provides data to support the hypothesis that individuals at increased risk of myocardial infarction may be prospectively identified by the presence of particular genotypes. If verified by others, genotype-specific risk assessment may join traditional coronary risk factors as a means to target preventive therapies. It should be noted that the genotypes identified in one population may not be applicable to other populations.


Yamada Y, Izawa H, Ichihara S, et al. Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. N Engl J Med. Dec 12, 2002;347:1916-1923.

Clinical Topics: Dyslipidemia, Prevention, Atherosclerotic Disease (CAD/PAD), Homozygous Familial Hypercholesterolemia, Hypertension, Smoking

Keywords: Spasm, Odds Ratio, Coronary Artery Disease, Myocardial Infarction, DNA, Risk Factors, Hypercholesterolemia, Smoking, Matrix Metalloproteinase 3, Hyperuricemia, Polymorphism, Genetic, Plasminogen, Genetic Predisposition to Disease, Confidence Intervals, Connexins, Colorimetry, Risk Assessment, Hypertension, Diabetes Mellitus, Logistic Models

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