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Investigating a decrease of risk alcoholism ADH allele in East Asian populations



Razib shares with us an overview of a new PLoS One paper which investigated the selection of an allele of alcohol dehydrogenase found in high frequency in some East Asian peoples. I gotta hand it to him for the snarky title of his post. Alcohol dehydrogenase is an enzyme that functions to break down alcohols which could otherwise be toxic. There are many classes of alcohol dehydrogenases. The specific allele in this study, ADH1b*47His, is associated with a decrease in the risk of alcoholism. How? These class of alcohol dehydrogenase (ADH) alleles expedite the metabolism of alcohols. Alleles that metabolize alcohols slower, such as the ADH2 and ADH3 variants, are associated with alcoholics.

The observation that ADH1b*47His is found in high frequencies in some East Asian populations have got Hui Li and coauthors curious to figure out if there has been some sort of selection to confer this decrease of alcoholism allele to be present in many peoples. They recently published their study in the free and open access journal, PLoS One. The research behind this paper, “Ethnic Related Selection for an ADH Class I Variant within East Asia,” involved looking at 30 different SNPs in the ADH gene of 24 different populations. It was observed that the unique ADH1b alleles correlated directly with ethnic groups, which I think is completely fascinating from an anthropological perspective.

In their population screen, it was observed that the ADH1b*47His allele is found highest in Korean-Japanese, Han Chinese, Hmong-Mien, Daic, and Austronesian people. Further, investigation of the ADH gene revealed that ADH1b*47His is actually a SNP that falls smack dab in the regulatory region of ADH. Regulatory regions are portions of a gene where promoters, inhibitors, and other transcription factors bind preferentially. Any alteration of these regions of genes ultimately effects how much product is made.

As Razib highlighted, the authors think that the real focus of selection may be the regulatory region. Well, no duh, the derived promoter allele probably increased expression levels of the enzyme and with more enzyme available, that ultimately helped people process alcohol more efficiently and faster. Clearly there’s a selective advantage to having more enzymes available to oxidize toxic agents. But the authors are a bit conservative in saying that detoxifying alcohol is primary reason why ADH1b*47His is present in high frequency in East Asian people. In fact, they suggest that ADH1 alleles have something to do with cancer, infectious diseases, etc. Makes sense, I mean these enzymes are detoxifying agents.

I know this post was heavy on population genetics, biochemistry and some physiology. I have to review that to some extent to give a background on ADH. I do want to point out again that this study yet again shows us that there are genetic differences between ethnic groups. Be it in ADH, or any other ancestry inherited marker, ethnic populations do exhibit some clearly definable genetic differences.