Morita Kazunori, Masuda Natsuki, Oniki Kentaro, Saruwatari Junji, Kajiwara Ayami, Otake Koji, Ogata Yasuhiro, Nakagawa Kazuko
Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
Japanese Red Cross Kumamoto Health Care Center, Kumamoto, Japan.
Toxicol Lett. 2015 Jul 16;236(2):117-22. doi: 10.1016/j.toxlet.2015.05.007. Epub 2015 May 12.
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 ALDH22 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 ALDH21/2 and 2/2 genotypes were two and three times higher, respectively, than in the never-smokers with the ALDH21/1 genotype. Moreover, the combined effect of smoking and the ALDH22 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 ALDH22 allele carriers. In addition, the ALDH22 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.
乙醛脱氢酶2（ALDH2）可对外源性和内源性有毒醛类进行解毒；然而，其对气道中香烟烟雾的保护作用尚不清楚。因此，我们研究了无活性的ALDH22等位基因是否与吸烟相关的慢性气道阻塞有关。我们进行了一项横断面研究，纳入了684名参加健康筛查项目的日本参与者，并在老年亚组中进行了一项回顾性纵向研究。携带ALDH21/2和2/2基因型的曾经吸烟者发生气道阻塞的风险分别是携带ALDH21/1基因型的从不吸烟者的两倍和三倍。此外，吸烟与ALDH22等位基因的联合作用在哮喘患者中尤为突出。在纵向关联分析中，ALDH2基因型与吸烟包年数的组合协同增加了气道阻塞的风险。仅在ALDH22等位基因携带者中，基线时的吸烟包年数被确定为气道阻塞的一个重要预测因素。此外，在Cox比例风险模型中，ALDH22等位基因也与吸烟相关气道阻塞的发生率有关。这项初步研究首次证明了ALDH2*2等位基因与香烟烟雾累积暴露之间在气道阻塞风险上存在显著的基因-环境相互作用。
