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Human adenylyl cyclase type 7 contains polymorphic repeats in the 3' untranslated region: investigations of association with alcoholism.

Platelet adenylyl cyclase activity has been proposed as a trait marker for alcoholism [Tabakoff et al. (1988): N Engl J Med 318:134-13;9; Parsian et al. (1996): Alcohol Clin Exp Res 20:745-751]. Human adenylyl cyclase type 7 (ADCY7) is a member of the adenylyl cyclase gene family, and it may be the major form of adenylyl cyclase expressed in human platelets. The published cDNA sequence of ADCY7 indicated the presence of potentially polymorphic regions in the 3' untranslated region of ADCY7. PCR techniques combined with fluorescently labeled primers were used to amplify two separate tetranucleotide repeat regions [(AACA)n] in the 3' untranslated region of ADCY7 from the genomic DNA of 62 unrelated individuals. The upstream (AACA)4-repeat was not polymorphic. Five different genotypes were found in the downstream (AACA)5-7 tetranucleotide repeat region. We also tested the association of the tetranucleotide polymorphism to alcohol dependence. When 30 alcoholic and 17 control individuals were compared, no difference was found in the ADCY7 tetranucleotide polymorphism between alcohol-dependent and control groups. Nevertheless, to our knowledge these are the first polymorphisms reported in an adenylyl cyclase gene. Adenylyl cyclases are important receptor-G protein-coupled effectors and are involved in numerous neuronal functions in the central nervous system. Whether variations in ADCY7 and possible variations in other members of this gene family are underlying other psychiatric disorders remains to be studied.