Combined effects of current-smoking and the aldehyde dehydrogenase 2*2 allele on the risk of myocardial infarction in Japanese patients

- Aldehyde dehydrogenase 2 (ALDH2) detoxifies toxic aldehydes in cigarette smoke.
- Current-smoking ALDH2*2 allele carriers were at risk of myocardial infarction (MI).
- Current-smoking and ALDH2*2 synergistically increased the peak creatine kinase.
- Current-smoking and ALDH2*2 synergistically increased triglycerides in MI subjects.

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 2220.2 IU/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.