Identification of Alcoholism Susceptibility Genes
Annual rept. 15 Sep 2002-15 Sep 2003
ERNEST GALLO CLINIC AND RESEARCH CENTEREMERYVILLE CA
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Genetic epidemiological analysis provides convincing data that a significant portion of the liability for developing alcoholism is inherited. The identity and mechanism by which genes contribute to inherited susceptibility to alcoholism are unknown. If genes that affect susceptibility to alcoholism can be identified, they are logical targets for the development of pharmacological agents to modify susceptibility and treat alcoholism. Primarily, the meiotic gene mapping approach has been used in an effort to identify genes that affect susceptibility to alcoholism. This approach may be insensitive to genes that have common alleles with modest effects on susceptibility. An alternative approach, allelic association analysis, may be far more powerful for detecting these genes, but requires that analysis of individual candidate genes. This proposal examines a large number of genes implicated in the biology of alcoholism to see whether common alleles of these genes affect susceptibility. Two hundred and fifty polymorphisms, in 21 candidate genes were genotyped in 1200 subjects from the UCSF family study and 600 subjects in 120 families with nicotine dependence have been successfully genotyped. An additional 140 previously reported polymorphism were found not to be informative in these populations. The most promising observation are that a common haploytpe of the adenylate cyclase type 2 gene is associated with a series of addiction related phenotypes p0.001-0.00001.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research