Department of Human Functional Genomics, Life Science Research Center, Mie University Gifu International Institute of Biotechnology Department of Cardiology, Gifu Prefectural Gifu Hospital Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital Department of Human Functional Genomics, Life Science Research Center, Mie University Department of Internal Medicine, Reimeikyo Rehabilitation Hospital Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine
Although lifestyle and environmental factors influence the prevalence of myocardial infarction, genetic epidemiological studies have suggested that several genetic variants increase the risk for this condition. We have performed a large-scale association study to identify gene polymorphisms for reliable assessment of the genetic risk of myocardial infarction. The study population comprised 3,483 unrelated Japanese individuals (1,913 men; 1,570 women), including 1, 192 subjects with myocardial infarction and 2,291 controls. The genotypes for 164 polymorphisms of 137 candidate genes were determined with an oligonucleotide ligation assay based on analysis of fluorescent microspheres with suspension array technology. Multivariable logistic regression analysis with adjustment for age, sex, body mass index, and the prevalence of smoking, hypertension, diabetes mellitus, and hypercholesterolemia revealed that the 677C → T (Ala222Val) polymorphism of MTHFR, the 1595C → G (Ser447Stop) polymorphism of LPL, and the -108/3G → 4G polymorphism of IPF1 were significantly associated with the prevalence of myocardial infarction. A stepwise forward selection procedure demonstrated that IPF1, MTHFR, and LPL genotypes significantly affected the prevalence of myocardial infarction. Combined genotype analysis of these polymorphisms yielded a maximum odds ratio of 2.54 for the combined genotype of TT for MTHFR, CC for LPL, and 3G3G for IPF1. The genotypes for MTHFR, LPL, and IPF1 may prove reliable for assessment of genetic risk for myocardial infarction. Determination of the combined genotype for these genes may contribute to primary, personalized prevention of this condition.
Journal Article / 学術雑誌論文
This article is not an exact copy of the original published article in Thrombosis and Haemostasis. The definitive publisher-authenticated version of Yamada, Yoshiji; Matsuo, Hitoshi; Segawa, Tomonori; Watanabe, Sachiro; Kato, Kimihiko; Hibino, Takeshi; Yokoi, Kiyoshi; Ichihara, Sahoko; Metoki, Norifumi; Yoshida, Hidemi; Satoh, Kei; Nozawa, Yoshinori. Assessment of genetic risk for myocardial infarction. Thrombosis and Haemostasis. 2006, 96(2), p. 220-227 is available online at: http://dx.doi.org/10.1160/TH06-02-0117.