The Bidirectional Effect of Defective ALDH2 Polymorphism and Disease Prevention

Despite the role of aldehyde dehydrogenase 2 (ALDH2) in the detoxification of endogenous aldehydes, the defective polymorphism (rs671), which is highly prevalent among East Asians, does not show a serious phenotype, such as congenital abnormality. However, unfavorable and favorable impacts of the variant allele, ALDH2*2, on various disease risks have been reported. The underlying mechanisms are often complicated due to the compensatory aldehyde detoxification systems. As the phenotypes emerge due to overlapping environmental factors (e.g., alcohol intake and tobacco smoke) or individual vulnerabilities (e.g., aging and apolipoprotein E ε4 allele), polymorphism is therefore considered to be important in the field of preventative medicine. For example, it is important to recognize that ALDH2*2 carriers are at a high risk of alcohol drinking-related cancers; however, their drinking habit has less adverse effects on physiological indices, such as blood pressure, body mass index, levels of lipids, and hepatic deviation enzymes in the blood, than in non-ALDH2*2 carriers. Therefore, opportunities to reconsider their excessive drinking habit before adverse events occur can be missed. To perform effective disease prevention, the effects of ALDH2*2 on various diseases and the biological mechanisms should be clarified.