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

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, r...

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Autores principales: Nakano, Yukiko, Ochi, Hidenori, Onohara, Yuko, Sairaku, Akinori, Tokuyama, Takehito, Matsumura, Hiroya, Tomomori, Shunsuke, Amioka, Michitaka, Hironomobe, Naoya, Motoda, Chikaaki, Oda, Nozomu, Chayama, Kazuaki, Chen, Che-Hong, Gross, Eric R., Mochly-Rosen, Daria, Kihara, Yasuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142328/
https://www.ncbi.nlm.nih.gov/pubmed/27927211
http://dx.doi.org/10.1186/s12929-016-0304-x
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author Nakano, Yukiko
Ochi, Hidenori
Onohara, Yuko
Sairaku, Akinori
Tokuyama, Takehito
Matsumura, Hiroya
Tomomori, Shunsuke
Amioka, Michitaka
Hironomobe, Naoya
Motoda, Chikaaki
Oda, Nozomu
Chayama, Kazuaki
Chen, Che-Hong
Gross, Eric R.
Mochly-Rosen, Daria
Kihara, Yasuki
author_facet Nakano, Yukiko
Ochi, Hidenori
Onohara, Yuko
Sairaku, Akinori
Tokuyama, Takehito
Matsumura, Hiroya
Tomomori, Shunsuke
Amioka, Michitaka
Hironomobe, Naoya
Motoda, Chikaaki
Oda, Nozomu
Chayama, Kazuaki
Chen, Che-Hong
Gross, Eric R.
Mochly-Rosen, Daria
Kihara, Yasuki
author_sort Nakano, Yukiko
collection PubMed
description 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. METHODS AND 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.
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spelling pubmed-51423282016-12-15 Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese Nakano, Yukiko Ochi, Hidenori Onohara, Yuko Sairaku, Akinori Tokuyama, Takehito Matsumura, Hiroya Tomomori, Shunsuke Amioka, Michitaka Hironomobe, Naoya Motoda, Chikaaki Oda, Nozomu Chayama, Kazuaki Chen, Che-Hong Gross, Eric R. Mochly-Rosen, Daria Kihara, Yasuki J Biomed Sci Research 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. METHODS AND 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. BioMed Central 2016-12-07 /pmc/articles/PMC5142328/ /pubmed/27927211 http://dx.doi.org/10.1186/s12929-016-0304-x Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Nakano, Yukiko
Ochi, Hidenori
Onohara, Yuko
Sairaku, Akinori
Tokuyama, Takehito
Matsumura, Hiroya
Tomomori, Shunsuke
Amioka, Michitaka
Hironomobe, Naoya
Motoda, Chikaaki
Oda, Nozomu
Chayama, Kazuaki
Chen, Che-Hong
Gross, Eric R.
Mochly-Rosen, Daria
Kihara, Yasuki
Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese
title Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese
title_full Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese
title_fullStr Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese
title_full_unstemmed Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese
title_short Genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B are associated with the etiology of atrial fibrillation in Japanese
title_sort genetic variations of aldehyde dehydrogenase 2 and alcohol dehydrogenase 1b are associated with the etiology of atrial fibrillation in japanese
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5142328/
https://www.ncbi.nlm.nih.gov/pubmed/27927211
http://dx.doi.org/10.1186/s12929-016-0304-x
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