To see how
ADH4 evolved, Benner's team read the stretches of DNA that make
ADH4 in 27 modern primate species, including lemurs, monkeys, apes and humans.
Polymorphism of the human alcohol dehydrogenase 4 (
ADH4) promoter affects gene expression.
When you look at persons who have the
ADH4 gene variant, they begin drinking very early.
For example, several studies found other variations in and near the ADH1B gene, as well as in or near the
ADH4, ADH1C, ADH5, ADH6, and ADH7 genes that affect risk for alcoholism or the level of alcohol consumption (see the article by Hurley and Edenberg, pp.
Some of the COGA victories include associations that have been subsequently substantiated by other investigations, such as GABA receptor alpha (GABRA2), cholinergic muscarinic 2 receptor (CHRM2), and
ADH4 (Edenberg and Froud 2006).
* The
ADH4 gene is expressed almost exclusively in the liver (Hurley et al.
Humans have seven different genes, called ADH1A, ADH1B, ADH1C,
ADH4, ADH5, ADH6, and ADH7, that encode medium-chain ADHs (see Table 1).
ADH1 (an enzyme variant [i.e., isozyme] belonging to the class I ADH) is the most efficient for this substrate,
ADH4 is about 10 times less efficient, and ADH3 is nearly inactive toward alcohol.
At high concentrations, alcohol is eliminated at a high rate because of the presence of enzyme systems with high activity levels ([K.sub.m]), (2) such as class II ADH, [[beta].sub.3]-ADH (encoded by
ADH4 and ADH1B genes, respectively) and CYP2E1 (Bosron et al.