title: Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese.
abstract: BACKGROUND
  Alcohol consumption and oxidative stress are well-known risk factors for developing atrial fibrillation (AF). Single nucleotide polymorphisms (SNPs) of alcohol dehydrogenase (ADH1B) and aldehyde dehydrogenase 2 (ALDH2) genes encoding enzymes of alcohol and reactive aldehyde metabolism, respectively, are prevalent among East Asians. Here, we examined whether these SNPs were associated with AF in Japanese patients.
  
  
  RESULTS
  Five hundred seventy-seven Japanese patients with AF undergoing catheter ablation and 1935 controls at Hiroshima University Hospital were studied. Alcohol consumption habits, medical history, electrocardiogram (EKG), electrophysiology and cardiac echocardiography were reviewed. Patients were also genotyped for ALDH2 (rs671) and ADH1B (rs1229984). A significant linear correlation was found between ALDH2 genotype and mean alcohol intake (P = 1.7 × 10-6). Further, ALDH2 (rs671) was associated with AF (P = 7.6 × 10-4, odds ratio [OR] = 0.6). Frequency of the ALDH2 SNP allele A which limits acetaldehyde metabolism was lower in patients with AF (18.8%) than in controls (23.5%). In contrast, we found that the frequencies of the ADH1B SNP genotypes were similar in patients with AF and in controls. Subset analysis among the 182 patients with lone AF and 914 controls (control II) (<60 years of age and without hypertension), both ALDH2 and ADH1B SNPs were significantly associated with AF (P = 0.013, OR = 0.7; P = 0.0007, OR = 1.4, respectively). The frequency of the dysfunctional allele A of ALDH2 was significantly lower and the dysfunctional allele G of ADH1B was significantly higher in patients with lone AF than in control II (ALDH2 A allele frequency = 0.176 vs 0.235, OR = 1.3, P = 0.013, ADH1B SNP G allele frequency = 0.286 vs 0.220, OR = 1.4, P = 0.0007).
  
  
  CONCLUSIONS
  When considering all patients enrolled, the dysfunctional ALDH2 allele was negatively associated with AF. When examining a subset of patients with lone AF, the dysfunctional ALDH2 allele was negatively associated with AF and the slower metabolizing ADH1B allele was positively associated with AF. Hence, prolonged metabolic conversion of alcohol to acetaldehyde may be associated with the occurrence of AF in the Japanese and other East Asian populations.
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.|Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, RIKEN, Hiroshima, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Nakano
authors.affiliation: Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, RIKEN, Hiroshima, Japan.|Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University , Hiroshima, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ochi
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Onohara
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Sairaku
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Takehito
authors.initials: T
authors.lastname: Tokuyama
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Hiroya
authors.initials: H
authors.lastname: Matsumura
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tomomori
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Amioka
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Hironomobe
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Chikaaki
authors.initials: C
authors.lastname: Motoda
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
authors.forename: Nozomu
authors.initials: N
authors.lastname: Oda
authors.affiliation: Laboratory for Digestive Diseases, Center for Integrative Medical Sciences, RIKEN, Hiroshima, Japan.|Department of Gastroenterology and Metabolism, Applied Life Science, Institute of Biomedical & Health Science, Hiroshima University , Hiroshima, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Department of Chemical & Systems Biology, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Che-Hong
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Chemical & Systems Biology, School of Medicine, Stanford University, Stanford, CA, USA.|Department of Anesthesiology, Perioperative and Pain Management, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gross
authors.affiliation: Department of Chemical & Systems Biology, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Daria
authors.initials: D
authors.lastname: Mochly-Rosen
authors.affiliation: Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical & Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. ykihara@hiroshima-u.ac.jp.
authors.forename: Yasuki
authors.initials: Y
authors.lastname: Kihara
mesh_terms: D000328:Adult; D000368:Aged; D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000428:Alcohol Drinking; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D044466:Asian People; D001281:Atrial Fibrillation / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D004452:Echocardiography; D004562:Electrocardiography; D005202:Asia, Eastern; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
chemical_list: C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: ADH1B; ALDH2; Alcohol; Atrial fibrillation; Single nucleotide polymorphism