title: Association of genetic variants with atrial fibrillation.
abstract: Recent genome-wide association studies (GWASs) identified various genes and loci that confer susceptibility to coronary artery disease or myocardial infarction among Caucasian populations. As myocardial ischemia is an important risk factor for atrial fibrillation, we hypothesized that certain polymorphisms may contribute to the genetic susceptibility to atrial fibrillation through affecting the susceptibility to coronary artery disease. The aim of the present study was to examine the possible association of atrial fibrillation in Japanese individuals with 29 polymorphisms identified as susceptibility loci for coronary artery disease or myocardial infarction in the meta-analyses of GWASs in Caucasian populations. The study subjects comprised 5,470 Japanese individuals (305 subjects with atrial fibrillation and 5,165 controls). Genotypes for 29 polymorphisms were determined by a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Comparisons of the allele frequencies by the χ2test revealed that rs599839 (G→A) of the proline/serine-rich coiled-coil 1 gene (PSRC1, P=0.0084) and rs11556924 (C→T, Arg363His) of the zinc finger, C3HC-type containing 1 gene (ZC3HC1, P=0.0076) were significantly (P<0.01) associated with atrial fibrillation. Multivariable logistic regression analysis with adjustment for age, gender, body mass index, estimated glomerular filtration rate, and the prevalence of smoking, hypertension, diabetes mellitus, and dyslipidemia revealed that rs599839 (P=0.0043; odds ratio, 1.56; dominant model) and rs11556924 (P=0.0043; odds ratio, 1.93; dominant model) were significantly associated with atrial fibrillation, with the minorGandTalleles, respectively, representing risk factors for this condition. PSRC1 and ZC3HC1 may thus be susceptibility loci for atrial fibrillation in Japanese individuals.
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507-8522, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yamase
authors.affiliation: Department of Internal Medicine, Meitoh Hospital, Nagoya, Aichi 465-0025, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507-8522, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Horibe
authors.affiliation: Department of Cardiovascular Medicine, Gifu Prefectural Tajimi Hospital, Tajimi, Gifu 507-8522, Japan.
authors.forename: Chikara
authors.initials: C
authors.lastname: Ueyama
authors.affiliation: Department of Cardiovascular Medicine, Inabe General Hospital, Inabe, Mie 511-0428, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Fujimaki
authors.affiliation: Department of Cardiology, Kasugai Municipal Hospital, Kasugai, Aichi 486-8510, Japan.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Oguri
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gifu 500-8717, Japan.
authors.forename: Masazumi
authors.initials: M
authors.lastname: Arai
authors.affiliation: Department of Cardiology, Gifu Prefectural General Medical Center, Gifu, Gifu 500-8717, Japan.
authors.forename: Sachiro
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Cardiology, Nagoya University Graduate School of Medicine, Nagoya, Aichi 466-8550, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Murohara
authors.affiliation: Department of Human Functional Genomics, Life Science Research Center, Mie University, Tsu, Mie 514-8507, Japan.
authors.forename: Yoshiji
authors.initials: Y
authors.lastname: Yamada
keywords: arrhythmia; atrial fibrillation; genetic variant; genetics; polymorphism