Morita Kazunori, Miyazaki Hiroko, Saruwatari Junji, Oniki Kentaro, Kumagae Naoki, Tanaka Takahiro, Kajiwara Ayami, Otake Koji, Ogata Yasuhiro, Arima Yuichiro, Hokimoto Seiji, Ogawa Hisao, 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 Jan 5;232(1):221-5. doi: 10.1016/j.toxlet.2014.11.014. Epub 2014 Nov 15.
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 ALDH22 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 ALDH22 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.
乙醛脱氢酶2（ALDH2）可解毒有毒醛类，如香烟烟雾中的乙醛；然而，吸烟状态与ALDH2基因型之间对冠状动脉疾病（CAD）的交互作用尚未见报道。我们研究了吸烟状态和ALDH2基因型的影响，并评估了它们对心肌梗死（MI）或稳定型心绞痛（SA）风险的交互作用和联合作用，研究对象包括221例MI患者、175例SA患者以及473名年龄和性别匹配的无CAD对照者。当前吸烟和ALDH22等位基因会增加MI风险（校正比值比4.54，95%置信区间2.25 - 9.15），尽管这种组合与SA风险无关。这种组合还会使急性心肌梗死（AMI）患者的肌酸激酶（CK）峰值水平协同升高。此外，发现当前吸烟是ALDH22等位基因携带者CK峰值水平升高的显著危险因素（B 2220.2IU/L，p = 0.008），而非携带者则不然。此外，在AMI患者中还发现这种组合对甘油三酯水平有协同作用。这些初步研究结果表明当前吸烟与无活性的ALDH2*2等位基因的组合可能会增加MI风险，并协同增加梗死面积。
