title: Association between the aldehyde dehydrogenase 2*2 allele and smoking-related chronic airway obstruction in a Japanese general population: a pilot study.
abstract: Aldehyde dehydrogenase 2 (ALDH2) detoxifies exogenous and endogenous toxic aldehydes; however, its protective effect against cigarette smoke in airways is unknown. We therefore examined whether the inactive ALDH2*2 allele is associated with smoking-related chronic airway obstruction. We conducted a cross-sectional study including 684 Japanese participants in a health screening program, and a retrospective longitudinal study in the elderly subgroup. The risks of airway obstruction in the ever-smokers with the ALDH2*1/*2 and *2/*2 genotypes were two and three times higher, respectively, than in the never-smokers with the ALDH2*1/*1 genotype. Moreover, the combined effect of smoking and the ALDH2*2 allele was prominent in the asthmatic subjects. In a longitudinal association analysis, the combination of the ALDH2 genotype and pack-years of smoking synergistically increased the risk of airway obstruction. The number of pack-years of smoking at baseline was identified to be a significant predictor of airway obstruction only in the ALDH2*2 allele carriers. In addition, the ALDH2*2 allele was also associated with the incidence of smoking-related airway obstruction, in the Cox proportional hazards model. This pilot study demonstrated for the first time a significant gene-environment interaction between the ALDH2*2 allele and cumulative exposure to cigarette smoke on the risk of airway obstruction.
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: Natsuki
authors.initials: N
authors.lastname: Masuda
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: 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: 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: 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; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D044466:Asian People / Q000235:genetics; D003430:Cross-Sectional Studies; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D007564:Japan; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology* / Q000235:genetics*; D012189:Retrospective Studies; D012907:Smoking / Q000009:adverse effects*
chemical_list: C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: Aldehydes; Asthma; Chronic obstructive pulmonary disease; Genetic association study; Longitudinal study