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Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese

Overview of attention for article published in Journal of Biomedical Science, December 2016
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Title
Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese
Published in
Journal of Biomedical Science, December 2016
DOI 10.1186/s12929-016-0304-x
Pubmed ID
Authors

Yukiko Nakano, Hidenori Ochi, Yuko Onohara, Akinori Sairaku, Takehito Tokuyama, Hiroya Matsumura, Shunsuke Tomomori, Michitaka Amioka, Naoya Hironomobe, Chikaaki Motoda, Nozomu Oda, Kazuaki Chayama, Che-Hong Chen, Eric R. Gross, Daria Mochly-Rosen, Yasuki Kihara

Abstract

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. 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). 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.

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Mendeley readers

The data shown below were compiled from readership statistics for 28 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 28 100%

Demographic breakdown

Readers by professional status Count As %
Other 4 14%
Student > Ph. D. Student 3 11%
Researcher 3 11%
Student > Postgraduate 3 11%
Professor > Associate Professor 3 11%
Other 6 21%
Unknown 6 21%
Readers by discipline Count As %
Medicine and Dentistry 10 36%
Biochemistry, Genetics and Molecular Biology 5 18%
Engineering 3 11%
Agricultural and Biological Sciences 1 4%
Unknown 9 32%