Genetic Variation Found to Protect Some Afro-Trinidadians from Alcoholism

Sherry Wasilow-Mueller and Mika Ono

A group of scientists at The Scripps Research Institute, the University of the West Indies, and the Indiana University School of Medicine has found that a specific genetic variation appears to protect some Afro-Trinidadians from developing alcoholism. However, the same variation may also increase the risk of liver disease if these individuals choose to drink.

The results are published in the February 2007 issue of Alcoholism: Clinical & Experimental Research, the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism.

Alcohol dehydrogenase (ADH) is one of the major enzymes involved in alcohol metabolism. Yet this enzyme is not identical in all people. Some individuals have genetic variations that lead to differences in the enzyme, and thus in the ability to metabolize alcohol.

In the recent study, the researchers investigated the effects of one of the known variations of the ADH gene, ADH1B*3, which has been found in people of African descent.Although ADH1B*3 was identified in Indianapolis 10 years ago, since that time few studies have been conducted on its role in drinking or the development of alcoholism.

To study the effect of ADH1B*3 on alcohol dependence, the research team turned to the Republic of Trinidad and Tobago, an island nation in the Caribbean comprised mainly of individuals of two separate ethnic groups of African and East Indian ancestry, respectively.

"Island populations often provide a unique opportunity to evaluate genetic factors as populations on these islands are often genetically 'isolated' for a number of generations," said Cindy Ehlers, associate professor at Scripps Research, who led the study. "These can provide a more homogenous environment when compared to large heterogeneous cultures such as the United States."

Study participants were recruited from the two major ethnic groups of Trinidad: 138 alcohol-dependent individuals, as well as 98 "controls" or non-alcohol-dependent individuals matched on age, gender, education, and ethnicity. Researchers assessed all participants using the Semi-Structured Assessment for the Genetics of Alcoholism in order to gather information on demographics, psychiatric diagnoses, personal drinking, and drug-use history. Each participant was genotyped at the ADH1B locus through a blood sample, and also provided a number of other health measures.

As predicted, the researchers discovered a relatively high prevalence—a full 41 percent—of the ADH1B*3 allele in Afro-Trinidadians. An allele is a member of a pair of genes, one inherited from each parent.

Significantly, the study found that, on average, individuals with at least one ADH1B*3 allele had lower alcohol consumption levels and were less likely to be alcohol dependent. However, individuals with the ADH1B*3 allele who were alcohol dependent tended to have elevated serum alanine aminotransferease levels, a measure of liver dysfunction.

"Having the ADH1B*3 allele provides some genetic protection from developing alcoholism, but it is not complete," noted Ehlers. "Individuals can choose to drink at high levels in spite of having some protection against alcoholism, just like individuals at high genetic risk for alcoholism can choose not to drink.  There are no genes for alcohol dependence like there are genes for Huntington's chorea or other single-gene disorders.  There are only genes that influence risk and protection for the disorder."

In addition to Ehlers, authors of the Alcoholism: Clinical & Experimental Research paper, "Association of the ADH1B*3 Allele with Alcohol Related Phenotypes in Trinidad," were: Karelia Montane-Jaime, Shelly Moore, and Samuel Shafe of the University of the West Indies; Roma Joseph of the San Fernando Hospital in Trinidad; and Lucinda G. Carr of Indiana University. 

The study was funded by the National Institute on Alcohol Abuse and Alcoholism, the Stein Endowment Fund, and the University of the West Indies.

Send comments to: mikaono[at]scripps.edu

"Having the ADH1B*3 allele provides some genetic protection from developing alcoholism, but it is not complete... There are no genes for alcohol dependence like there are genes for Huntington's chorea or other single-gene disorders. There are only genes that influence risk and protection for the disorder."

—Cindy Ehlers