- The gene CYP2E1, which is located on the terminal region of chromosome 10, plays a major role in the metabolic processing of alcohol
- New findings show that this gene is linked with a low sensitivity to alcohol and increased risk for alcoholism
- CYP2E1 could therefore be used as a predictor for those who are at risk for alcoholism
The research into how alcohol reacts with the brain is a complex one, and has been relentlessly studied for many years. But a new study has shown, through linkage and association analysis on various family groups, that a gene originally thought to be primarily associated with ethanol metabolism, may be significantly involved in dictating an individual's alcohol sensitivity.
The results will be published in the January 2011 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.
According to Kirk Wilhelmsen, one of the author's of the study and Professor at the University of North Carolina at Chapel Hill's Department of Genetics and Neurology, the researchers were led to the CYP2E1 gene because it was at the terminal end of chromosome 10, which was the region in which linkage was detected.
"Linkage asks the question, in this case for the whole genome, whether siblings that have similar (or different) phenotypes have inherited the same (or different) chromosomes from their parents," says Wilhelmsen. "What is important about these studies is the strength of association is very strong compared to the vast majority of associations between DNA variations and behavioral traits."
Wilhelmsen added that due to CYP2E1's terminal position on the chromosome, and the tendency regions of other chromosomes to swap small sections of DNA (in a process called crossing over), there are three distinct haplotypes of the gene. "We can make predictions about the level of response to alcohol an individual will have based on determining which haplotypes an individual has," he said. "Figuring out which specific variations are important would be icing on the cake. It is likely that a combination of variations is what is important."
The data was collected from 237 college student siblings that had one alcohol-dependent parent, but were not dependent themselves. This allowed the researchers to explore an area of little research, which is the relationship between the genetics of an individual and their alcoholic behavior.
"Alcoholism is a genetically influenced behavior, but gene discovery for behavior diseases are difficult for many reasons," said David Goldman, the Chief of the Lab of Neurogenetics at the National Institute on Alcohol Abuse and Alcoholism. "Even if one gene is important, as now appears to be the case for this metabolic gene CYP2E1, there may be multiple functional variants in the gene. We probably don't even know the identities of the players."
Goldman also added that this discovery while important in establishing a possible genetic predictor for alcoholism, there are still many questions left unanswered that can only be solved by more research into the area.
Wilhelmsen agreed. "[But] what is much more important than knowing this piece of information is that this suggests how our brains sense alcohol. The identification of CYP2E1 suggests three mechanisms."
"Two of these mechanisms are paradigm changers," he said. "The most exciting possibility is that this result indicates that alcohol induces production of more free radicals in the brain in people that are more sensitive to alcohol."
Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "The Investigation of CYP2E1 in Relation to the Level of Response to Alcohol Through a Combination of Linkage and Association Analysis," were Amy Webb of the Department of Biomedical Engineering at the University of North Carolina at Chapel Hill, Penelope A. Lind of the Queensland Institute of Medical Research in Brisbane, Australia, Heidi S. Feiler at the Lawrence Berkeley National Laboratory, Life Sciences Division at Berkeley, California, and from the University of California Department of Psychiatry in San Diego: Jelger Kalmijn, Tom L. Smith and Marc A.Schuckit. The study was supported by funds provided by the State of California for medical research on alcohol and substance abuse through the University of California, San Francisco, the Veterans Affairs Research Service, and grants from the National Institute on Alcohol Abuse and Alcoholism, the CompassPoint Addiction Foundation, and the Bowles Center for Alcohol Studies at UNC. This release is supported by the Addiction Technology Transfer Center Network at http://www.