The best-known functional ADH variant is the rs1229984 polymorphism (Arg48His), associated with the ADH1B*2 allele, which produces an enzyme with higher catalytic activity for converting ethanol to acetaldehyde. The ADH1B*3 variant (rs2066702) has been shown to exhibit lower activity compared to ADH1B*2. ADH1C shows two major functional variants, ADH1C*1 (rs1693482) and ADH1C*2 (rs698), that encode for isoforms that differ in in vitro activity, with the ADH1C*1 showing 1.5- to 2-fold greater activity than ADH1C*2 (113). There are additional genetic variations identified in non-coding regions of ADH genes, such as ADH4, that have been associated with altered gene expression as well as AUD risk, however, the effect of these variations on ADH activity and overall metabolism remains to be established (113, 169, 170).
