[Importance of an Aldehyde Dehydrogenase 2 Polymorphism in Preventive Medicine]

Unlike genetic alterations in other aldehyde dehydrogenase (ALDH) isozymes, a defective ALDH2 polymorphism (rs671), which is carried by almost half of East Asians, does not show a clear phenotype such as a shortened life span. However, impacts of a defective ALDH2 allele, ALDH2*2, on various disease risks have been reported. As ALDH2 is responsible for the detoxification of endogenous aldehydes, a negative effect of this polymorphism is predicted, but bidirectional effects have been actually observed and the mechanisms underlying such influences are often complex. One reason for this complexity may be the existence of compensatory aldehyde detoxification systems and the secondary effects of these systems. There are many issues to be addressed with regard to the ALDH2 polymorphism in the field of preventive medicine, including the following concerns. First, ALDH2 in the fetal stage plays a role in aldehyde detoxification; therefore, prenatal health effects of environmental aldehyde exposure are of concern for ALDH2*2-carrying fetuses. Second, ALDH2*2 carriers are at high risk of drinking-related cancers. However, their drinking habits result in less worsening of physiological findings, such as energy metabolism index and liver functions, compared with non-ALDH2*2 carriers, and therefore opportunities to detect excessive drinking can be lost. Third, personalized medicine such as personalized prescriptions for ALDH2*2 carriers will be required in the clinical setting, and accumulation of evidence is awaited. Lastly, since the ALDH2 polymorphism is not considered in workers' limits of exposure to aldehydes and their precursors, efforts to lower exposure levels beyond legal standards are required.