title: Combined effects of current-smoking and the aldehyde dehydrogenase 2*2 allele on the risk of myocardial infarction in Japanese patients.
abstract: Aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes, e.g. acetaldehyde in cigarette smoke; however, the interactive effects between smoking status and the ALDH2 genotype on coronary artery disease (CAD) have not been reported. We investigated the effects of smoking status and the ALDH2 genotype, and assessed their interactive and combined effects on the risk of myocardial infarction (MI) or stable angina (SA), including 221 MI and 175 SA subjects and 473 age- and sex-matched controls without CAD. Current-smoking and the ALDH2*2 allele additively increased the risk of MI (adjusted odds ratio 4.54, 95% confidence interval 2.25-9.15), although this combination was not associated with the risk of SA. This combination also increased the peak creatine kinase (CK) level synergistically in the acute MI (AMI) subjects. Moreover, current-smoking was found to be a significant risk factor for an increased peak CK level in the ALDH2*2 allele carriers (B 2220.2IU/L, p=0.008), but not the non-carriers. Additionally, a synergistic effect of this combination on the triglycerides levels was also found in the AMI subjects. These preliminary findings suggest that the combination of current-smoking and the inactive ALDH2*2 allele may increase the risk of MI additively and the infarct size synergistically.
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Morita
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Miyazaki
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Saruwatari
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Oniki
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kumagae
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Ayami
authors.initials: A
authors.lastname: Kajiwara
authors.affiliation: Japanese Red Cross Kumamoto Health Care Center, Kumamoto, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Otake
authors.affiliation: Japanese Red Cross Kumamoto Health Care Center, Kumamoto, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ogata
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Arima
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Hokimoto
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Life Sciences, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan; Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan. Electronic address: kazukon@gpo.kumamoto-u.ac.jp.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000368:Aged; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D003402:Creatine Kinase / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D059647:Gene-Environment Interaction; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007564:Japan; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000201:enzymology / Q000208:ethnology / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects* / Q000208:ethnology; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D014280:Triglycerides; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D003402:Creatine Kinase
keywords: Aldehyde dehydrogenase 2; Myocardial infarction; Smoking; Stable angina; Triglycerides