Genetic epidemiology of ethanol metabolic enzymes: a role for selection

Human ethanol consumption has a profound impact on nutritional status, causing major alterations in intermediary metabolism and critical deficiencies of vitamins and trace elements. The major enzyme systems responsible for the principal steps in ethanol metabolism have been characterized and the genes cloned, and significant functional polymorphisms have been identified. An inactive allele of the mitochondrial ALDH is associated with flushing and reduced alcohol intake. This allele may also confer greater sensitivity to some of ethanol's toxic effects. In populations not possessing this variant, twin and adoptive studies have revealed that heritability for alcoholism is greater than 50%. The occurrence of three functional polymorphisms in the ethanol metabolic pathway, including two mutations which are conserved across populations, suggests a role for selection in their maintenance. The two general categories of selective forces to maintain these polymorphisms are food toxins and infectious diseases. Of the infectious agents, amoebi and other anaerobic and microaerophilic organisms of the gut are the most logical candidates.