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

Yoshiji Yamada, Hideo Izawa, Sahoko Ichihara, Fumimaro Takatsu, Hitoshi Ishihara, Haruo Hirayama, Takahito Sone, Masashi Tanaka, Mitsuhiro Yokota

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Abstract

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-scalestudy 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.

Original languageEnglish
Pages (from-to)1916-1923
Number of pages8
JournalNew England Journal of Medicine
Volume347
Issue number24
DOIs
Publication statusPublished - 12-12-2002
Externally publishedYes

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Myocardial Infarction
Genes
Matrix Metalloproteinase 3
Plasminogen Activator Inhibitor 1
Logistic Models
Genotype
Regression Analysis
Colorimetry
Hyperuricemia
DNA Primers
DNA Probes
Primary Prevention
Hypercholesterolemia
Epidemiologic Studies
Diabetes Mellitus
Body Mass Index
Fluorescence
Smoking
Alleles
Hypertension

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Yamada, Y., Izawa, H., Ichihara, S., Takatsu, F., Ishihara, H., Hirayama, H., ... Yokota, M. (2002). Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. New England Journal of Medicine, 347(24), 1916-1923. https://doi.org/10.1056/NEJMoa021445
Yamada, Yoshiji ; Izawa, Hideo ; Ichihara, Sahoko ; Takatsu, Fumimaro ; Ishihara, Hitoshi ; Hirayama, Haruo ; Sone, Takahito ; Tanaka, Masashi ; Yokota, Mitsuhiro. / Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. In: New England Journal of Medicine. 2002 ; Vol. 347, No. 24. pp. 1916-1923.
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abstract = "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-scalestudy 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.",
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Yamada, Y, Izawa, H, Ichihara, S, Takatsu, F, Ishihara, H, Hirayama, H, Sone, T, Tanaka, M & Yokota, M 2002, 'Prediction of the risk of myocardial infarction from polymorphisms in candidate genes', New England Journal of Medicine, vol. 347, no. 24, pp. 1916-1923. https://doi.org/10.1056/NEJMoa021445

Prediction of the risk of myocardial infarction from polymorphisms in candidate genes. / Yamada, Yoshiji; Izawa, Hideo; Ichihara, Sahoko; Takatsu, Fumimaro; Ishihara, Hitoshi; Hirayama, Haruo; Sone, Takahito; Tanaka, Masashi; Yokota, Mitsuhiro.

In: New England Journal of Medicine, Vol. 347, No. 24, 12.12.2002, p. 1916-1923.

Research output: Contribution to journalArticle

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T1 - Prediction of the risk of myocardial infarction from polymorphisms in candidate genes

AU - Yamada, Yoshiji

AU - Izawa, Hideo

AU - Ichihara, Sahoko

AU - Takatsu, Fumimaro

AU - Ishihara, Hitoshi

AU - Hirayama, Haruo

AU - Sone, Takahito

AU - Tanaka, Masashi

AU - Yokota, Mitsuhiro

PY - 2002/12/12

Y1 - 2002/12/12

N2 - 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-scalestudy 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.

AB - 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-scalestudy 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.

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