**7. The genetics of alcohol metabolism**

Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are the main enzymes of alcohol metabolism. Both the enzymes have several forms encoded by different genes. Enzymes with different characteristics having different ethnic distributions are because of variants of these genes. Since these enzyme variants work efficiently than others suggesting some people can metabolize alcohol more quickly, for example, a fast ADH enzyme or a slow ALDH enzyme may increase acetaldehyde level resulting in deleterious health effects including alcohol dependence [34].

A null allele is a mutant copy of a gene at a locus that completely lack normal function. This can result in to complete absence of the gene product (protein, RNA), or the expression of a non-functional gene product. At the phenotypic level, a null allele is indistinguishable from a deletion of the entire locus [35].

Because of genetic difference in these enzymes, alcohol related problems are either higher or lower in some ethnic groups, for example, *ADH1B\*2*, a variant of ADH is common in people of China, Japan and Korea but rare in Europe and Africa [36]. Another version of the ADH enzyme *ADH1B\*3*, occurs in 15–25% of African Americans [37]. These enzymes protect against alcoholism [38] by elevating the level of acetaldehyde that make drinking unpleasant [39]. Two variations of the ALDH enzyme, *ALDH1A1\*2* and *ALDH1A1\*3*, may be associated with alcoholism in African-American people [40].

Along with genetic factors, environmental factors are also important for alcoholism and alcohol-related health problems, for example, alcohol consumption increased from 2.5 to 13% in Japanese alcoholics who carried the protective ADH1B\*2 gene [41]. There is no difference in the rate of alcohol metabolism and enzyme pattern between Native Americans and Whites, more Native American people die of alcoholism than any other ethnic group in the United States [42]. This suggests that a rate of alcoholism and alcohol-related problems depends on environmental and genetic factors.
