Association of alcohol craving with alpha-synuclein (SNCA)

Background: Studies have found that genomic variation in the gene SNCA, which encodes the protein a-synuclein, may contribute to the variation in alcohol consumption in an inbred rat model of alcohol preference. Studies in humans have provided support for an association between SNCA and craving for alcohol. Methods: To examine the role of this gene in alcohol dependence and related phenotypes, 30 single nucleotide polymorphisms (SNPs) were genotyped across the SNCA gene in a sample of 219 multiplex alcoholic families of European American descent. Two phenotypes, alcohol dependence and alcohol craving, were analyzed using the pedigree disequilibrium test. Results: There was no evidence of association between any of the SNCA SNPs and alcohol dependence (p � 0.13). In contrast, 8 SNPs provided evidence of association (po0.05) with the phenotype of alcohol craving. Haplotype analysis further supported evidence of an association with alcohol craving; a haplotype encompassing SNPs in intron 4 through the region downstream of the gene was overtransmitted to cravers and a second haplotype was overtransmitted to noncravers. Conclusions: These results suggest that variation in SNCA contributes to alcohol craving, a common, although not uniform, feature of alcohol dependence.