Association of six genetic variants with myocardial infarction

Matsuoka,Reiko; Abe,Shintaro; Tokoro,Fumitaka; Arai,Masazumi; Noda,Toshiyuki; Watanabe,Sachiro; Horibe,Hideki; Fujimaki,Tetsuo; Oguri,Mitsutoshi; Kato,Kimihiko; Minatoguchi,Shinya; Yamada,Yoshiji

doi:10.3892/ijmm.2015.2115

Association of six genetic variants with myocardial infarction

Authors:
- Reiko Matsuoka
- Shintaro Abe
- Fumitaka Tokoro
- Masazumi Arai
- Toshiyuki Noda
- Sachiro Watanabe
- Hideki Horibe
- Tetsuo Fujimaki
- Mitsutoshi Oguri
- Kimihiko Kato
- Shinya Minatoguchi
- Yoshiji Yamada
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Affiliations: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu 500-8717, Japan, Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi 507-8522, Japan, Department of Cardiovascular Medicine, Inabe General Hospital, Inabe 511-0428, Japan, Department of Cardiology, Japanese Red Cross Nagoya First Hospital, Nagoya 453-8511, Japan, Department of Internal Medicine, Meitoh Hospital, Nagoya 465-0025, Japan, Department of Cardiology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan, Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu 514-8507, Japan
Published online on: February 27, 2015 https://doi.org/10.3892/ijmm.2015.2115
Pages: 1451-1459

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Abstract

Although various genes that confer susceptibility to myocardial infarction (MI) have been identified for Caucasian populations in genome-wide association studies (GWAS), genetic variants related to this condition in Japanese individuals have not been identified definitively. The aim of the present study was to examine an association of MI in Japanese individuals with 29 polymorphisms identified as susceptibility loci for MI or coronary artery disease in Caucasian populations by meta-analyses of GWAS. The study subjects comprised 1,824 subjects with MI and 2,329 controls. Genotypes of the polymorphisms were determined by Luminex bead-based multiplex assay. To compensate for multiple comparisons, we adopted the criterion of a false discovery rate (FDR) of <0.05 for statistical significance for association. Comparisons of allele frequencies by the χ2 test revealed that rs9369640 of the phosphatase and actin regulator 1 gene (PHACTR1, FDR=0.0007), rs4977574 of the CDKN2B antisense RNA 1 gene (CDKN2B-AS1, FDR=0.0038), rs264 of the lipoprotein lipase gene (LPL, FDR=0.0061), rs599839 of the proline/serine-rich coiled-coil 1 gene (PSRC1, FDR=0.0118), rs9319428 of the fms-related tyrosine kinase 1 gene (FLT1, FDR=0.0118) and rs12413409 of the cyclin and CBS domain divalent metal cation transport mediator 2 gene (CNNM2, FDR=0.0300) were significantly associated with MI. Multivariate logistic regression analysis with adjustment for covariates revealed that rs9369640 (P=0.0005; odds ratio, 0.89), rs4977574 (P=0.0001; odds ratio, 1.50), rs264 (P=0.0405; odds ratio, 0.85), rs599839 (P=0.0003; odds ratio, 0.68), rs9319428 (P=0.0155; odds ratio, 1.20) and rs12413409 (P=0.0076; odds ratio, 0.66) were significantly (P<0.05) associated with MI. PHACTR1, CDKN2B-AS1, LPL, PSRC1, FLT1 and CNNM2 may thus be susceptibility loci for MI in Japanese individuals.

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