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Gene variant predicts medication response in patients with alcohol dependence
Date:2/7/2008

Of the original 1383 COMBINE Study participants, 1013 were available to be genotyped for the current study, conducted by Raymond F. Anton, M.D., Medical University of South Carolina, and other COMBINE Study principal investigators in collaboration with David Goldman, M.D., and his colleagues in NIAAA's Laboratory of Neurogenetics. The researchers successfully genotyped 911 of the available patients and conducted their initial analysis in 604 who are white, 135 of whom were found to carry the genetic variant. Approximately 15 to 25 percent of humans carry the variant, with considerable variation among ethnicities.

As in the COMBINE clinical trial, drinking variables evaluated in the pharmacogenetic study included the percentage of days abstinent from alcohol, the percentage of heavy drinking days, and clinical outcome during 16 weeks of active treatment. In addition to naltrexone or placebo, all patients received medical management (nine brief, structured outpatient sessions delivered by a health professional) and some also received a combined behavioral intervention (integrated cognitive-behavioral and motivational enhancement therapies, together with techniques to enhance mutual-help participation).

The researchers found that, compared with patients who do not carry the variant, white variant carriers who received naltrexone fared substantially better than other groups on all measures, including almost a 6 times greater likelihood of good clinical outcome. Extending the clinical outcome measure to variant carriers of all ethnicities reduced the benefit to just over a 3 times greater likelihood of good outcome. The researchers found no gene-medication interaction in patients who received specialized alcohol counseling, leading to them to conclude that genotyping for the variant may be most useful when naltrexone is used without intensive counseling.

Approved by the U.S. Food and Drug Administration in 1994, naltrexone is one o
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Contact: Ann Bradley
abradley@mail.nih.gov
301-443-0595
NIH/National Institute on Alcohol Abuse and Alcoholism
Source:Eurekalert

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