Prediction of the risk of myocardial infarction from polymorphisms in candidate genes.
BACKGROUND
Although epidemiologic studies have suggested that several genetic variants increase the risk of myocardial infarction, large-scale association studies that examine many polymorphisms simultaneously are required to allow reliable prediction of the genetic risk of myocardial infarction.


METHODS
We used a fluorescence- or colorimetry-based allele-specific DNA-primer-probe assay system to determine the genotypes of 112 polymorphisms of 71 candidate genes in 2819 unrelated Japanese patients with myocardial infarction (2003 men and 816 women) and 2242 unrelated Japanese controls (1306 men and 936 women).


RESULTS
In an initial screening of the 112 polymorphisms for an association with myocardial infarction in 909 subjects, 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. In a large-scale study involving the selected polymorphisms and the remaining 4152 subjects, similar logistic-regression analysis revealed that the risk of myocardial infarction was significantly associated with the C1019T polymorphism in the connexin 37 gene (P<0.001) in men and the 4G-668/5G polymorphism in the plasminogen-activator inhibitor type 1 gene (P<0.001) and the 5A-1171/6A polymorphism in the stromelysin-1 gene (P<0.001) in women.


CONCLUSIONS
Determination of the genotypes of the connexin 37, plasminogen-activator inhibitor type 1, and stromelysin-1 genes may prove reliable in predicting the genetic risk of myocardial infarction and might thus contribute to the primary prevention of this condition.
Yamada
Yoshiji
Y
Department of Gene Therapy, Gifu International Institute of Biotechnology, Mitake, Japan.
Izawa
Hideo
H
Ichihara
Sahoko
S
Takatsu
Fumimaro
F
Ishihara
Hitoshi
H
Hirayama
Haruo
H
Sone
Takahito
T
Tanaka
Masashi
M
Yokota
Mitsuhiro
M
D016022:Case-Control Studies; D017630:Connexins / Q000235:genetics*; D015342:DNA Probes; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D000097006:Gap Junction alpha-4 Protein
D017630:Connexins; D015342:DNA Probes; D019278:Matrix Metalloproteinase 3; D017395:Plasminogen Activator Inhibitor 1; D000097006:Gap Junction alpha-4 Protein