Emerging Associations of the ALDH2*2 Polymorphism with Disease Susceptibility

Approximately eight percent of the world’s population inherits a point mutation in the Aldehyde Dehydrogenase-2 (ALDH2) gene. This polymorphism, referred to as ALDH2*2, is most prevalent in those ofEast Asian descent (Chinese, Japanese, Korean, and Taiwanese) and is rarelydetected in non-Asian individuals. Because of this genetic variation, roughly 560 million people worldwide are particularly susceptible to alcohol intoxication. The ALDH2*2 polymorphism encodes an inactivating, non-conservative amino acid substitution within the mitochondrial aldehyde dehydrogenase gene product. 

An extensive body of literature has accumulated to describe the molecular underpinnings of the ALDH2*2 alcohol sensitivity phenotype and has revealed a compelling exemplar of an enzymatically dominant negative polymorphic gene product. Recent data suggests, however, thatsensitivity to alcohol intoxication may be only one of many susceptibilities ofALDH2*2 carriers. Here, we review the available published data concerning the role of ALDH2 in ethanol metabolism and associated phenotypic effects of ALDH2*2 polymorphism. We also point to a growing body of literature implicating ALDH2 in such diverse health effects as cancer, osteoporosis, and heart disease.