Assessment of genetic risk for myocardial infarction

Yoshiji Yamada; Hitoshi Matsuo; Tomonori Segawa; Sachiro Watanabe; Kimihiko Kato; Takeshi Hibino; Kiyoshi Yokoi; Sahoko Ichihara; Norifumi Metoki; Hidemi Yoshida; Kei Satoh; Yoshinori Nozawa

doi:10.1160/TH06-02-0117

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(02): 220-227
DOI: 10.1160/TH06-02-0117

New Technologies, Diagnostic Tools and Drugs

Schattauer GmbH

Assessment of genetic risk for myocardial infarction

Yoshiji Yamada

¹Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan

²Gifu International Institute of Biotechnology, Kakamigahara, Japan

,

Hitoshi Matsuo

³Department of Cardiology, Gifu Prefectural Gifu Hospital, Gifu, Japan

,

Tomonori Segawa

³Department of Cardiology, Gifu Prefectural Gifu Hospital, Gifu, Japan

,

Sachiro Watanabe

³Department of Cardiology, Gifu Prefectural Gifu Hospital, Gifu, Japan

,

Kimihiko Kato

⁴Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan

,

Takeshi Hibino

⁴Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan

,

Kiyoshi Yokoi

⁴Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Japan

,

Sahoko Ichihara

¹Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Japan

,

Norifumi Metoki

⁵Department of Internal Medicine, Reimeikyo Rehabilitation Hospital, Minamitsugaru, Japan

,

Hidemi Yoshida

⁶Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan

,

Kei Satoh

⁶Department of Vascular Biology, Institute of Brain Science, Hirosaki University School of Medicine, Hirosaki, Japan

,

Yoshinori Nozawa

²Gifu International Institute of Biotechnology, Kakamigahara, Japan

› Author Affiliations

Abstract

Summary

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 performeda 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 yieldeda 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.

Keywords

Genetics - polymorphism - myocardial infarction - coronary heart disease - atherosclerosis

Full Text

References

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