title: Assessment of genetic risk for myocardial infarction.
abstract: 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.
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514-8507, Japan. yamada@gene.mie-u.ac.jp
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Matsuo
authors.forename: Tomonori
authors.initials: T
authors.lastname: Segawa
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hibino
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yokoi
authors.forename: Sahoko
authors.initials: S
authors.lastname: Ichihara
authors.forename: Norifumi
authors.initials: N
authors.lastname: Metoki
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Kei
authors.initials: K
authors.lastname: Satoh
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nozawa
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005456:Fluorescent Dyes / Q000494:pharmacology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008863:Microspheres; D008875:Middle Aged; D008957:Models, Genetic; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000235:genetics*; D011110:Polymorphism, Genetic; D012044:Regression Analysis; D012306:Risk
chemical_list: D005456:Fluorescent Dyes; D042965:Methylenetetrahydrofolate Reductase (NADPH2)