NO ALLELIC ASSOCIATION OF AN EXON-13 POLYMORPHISM OF THE GS-ALPHA GENE TO ALCOHOL AND OR DRUG-DEPENDENCE/

The adenylyl cyclase signal transduction system, a ubiquitous second m essenger system, has been identified as a potential marker for genetic risk of alcohol and drug dependence. Using the polymerase chain react ion (PCR) to amplify exon 13 of the Gs alpha gene, two alleles were di stinguished by denaturing gradient gel electrophoresis. One allele, de signed A(1), contained the previously published C in the codon for asp aragine 371, while the second allele, designated A(2), contains a C-T transition that conserves the asparagine residue at codon 371. The neu tral polymorphism eliminates a Fok I restriction enzyme cleavage site, allowing use of restriction fragment length polymorphisms of PCR prod ucts to determine allelic frequency in 235 subjects with alcohol and/o r drug dependence and in 85 control subjects. Since allele frequencies differ significantly by race, conparisons between affected individual s and controls were conducted separately for white and black groups. W ithin race, there were no significant differences in the frequency of the A(2) allele among alcoholics, subjects dependent on cocaine or opi oids, subjects dependent on these drugs and alcohol, and controls. We conclude that there is no association between alcohol and/or drug depe ndence and alleles of an exon 13 polymorphism of the Gsa gene in eithe r black or white individuals.