Opinions - Sequence Variation In The Alpha Synuclein Gene Contributes To Alcohol Craving

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- The protein alpha synuclein (SNCA) plays an important role in the regulation of dopamine function.

- Craving is a common symptom in alcoholics.

- New findings show that sequence variation in the gene that encodes SNCA contributes to whether or not an individual craves or does not crave alcohol.

The protein alpha synuclein (SNCA) plays an important role in the regulation of dopamine function. SNCA mutations can lead to significant problems, such as the neurodegenerative disorder Parkinson's disease, which is caused by a substantially reduced production of dopamine. New findings show that sequence variation in the SNCA gene also contributes to whether or not an individual craves or does not crave alcohol.

Results are published in the April issue of Alcoholism: Clinical & Experimental Research.

"Several years ago," explained Tatiana M. Foroud, director of the division of hereditary genomics at the Indiana University School of Medicine, "animal researchers identified a gene called SNCA, which appeared to contribute to the alcohol-drinking patterns of specially bred rats. Further studies have shown that different levels of SNCA exist in the brains of rodents that prefer alcohol versus those who do not like alcohol."

Since then, added corresponding-author Foroud, human research has suggested that SNCA might be important in determining an individual's craving for alcohol. "Using previous research as a building base," she said, "we utilized a large sample, a different type of analysis technique, and genotyped more sequence variants in the gene to provide a more comprehensive survey of the role of this gene in the craving for alcohol and alcoholism."

Foroud and her colleagues examined a sample of 219 alcoholic families of European American descent. Thirty single nucleotide polymorphisms (SNPs) were genotyped across the SNCA gene, and two phenotypes - alcohol dependence and alcohol craving - were also analyzed.

Although findings indicate no association between any of the SNCA SNPs and alcohol dependence, eight SNPs did have an association with alcohol craving.

"This strongly suggests that sequence variation in SNCA contributes to whether an individual craves or does not crave alcohol," said Foroud. "Interestingly, we found that this association cannot be expanded to everyone who has alcohol dependence. Rather, it seems to be limited to that subset of alcoholics who also indicate that they crave alcohol when they do not have the ability to obtain it."

"The strongest evidence for association was observed in a region encompassing one particular end of the gene," said Alison Goate, professor of psychiatry, genetics and neurology, at Washington University. "This is interesting because it appears to confirm a previous association between SNPs in the same region of the rat SNCA gene that differ between alcohol-preferring and non-preferring rats. It is this subgroup of alcoholics who have cravings that seem to be influenced by variation in the SNCA gene."

Foroud said that this study supports the emerging belief in the alcohol-research field that there are "subtypes" of alcoholics, in this case, a subset of individuals in whom variation in SNCA is an important contributor to the risk of developing alcoholism.

"Understanding the role of SNCA in sensitivity to craving may enable the future development of drugs to help alleviate the symptoms of craving," added Goate, "improving the chances that an individual might be able to stop drinking."

"Alcoholism is a complex disorder and we are identifying pieces of the puzzle that help us to understand why some individuals develop alcohol dependence and others do not," said Foroud. "The role of SNCA is only one of these pieces."

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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, "Association of Alcohol Craving with Alpha Synuclein (SNCA)," were: Leah Flury Wetherill, Tiebing Liang, John Nurnberger, Jr., Lucinda Carr, Xiaoling Xuei, and Howard J. Edenberg of Indiana University School of Medicine; Danielle M. Dick of Washington University School of Medicine; Victor Hesselbrock of the University of Connecticut School of Medicine; John Kramer of the University of Iowa Carver College of Medicine; Marc Schuckit of the University of California, San Diego; and Bernice Porjesz of SUNY Health Sciences Center. The study was funded by the Technology Fund, and the Indiana Genomics Initiative.

Contact: Tatiana M. Foroud, Ph.D.
Indiana University School of Medicine

Alison Goate, D. Phil.
Washington University, St. Louis

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