Association study between genetic polymorphisms in the 14-3-3 η chain and dopamine D4 receptor genes and alcoholism

Background: The dopaminergic system may be involved in the development of alcoholism. As part of our ongoing studies on the association between alcoholism and dopaminergic genes, we report herein a mutation analysis of the 14-3-3 eta chain gene (YWHAH) and an association study between alcoholism and the YWHAH and dopamine D4 receptor gene (DRD4) polymorphisms. Methods: Nucleotide mutations were investigated using single-strand conformation polymorphism methods. Associations were analyzed using a case-control design involving 185 Japanese alcoholics and 286 Japanese controls. Results: Five polymorphisms, -147G>A, -134(GCCTGCA)2-4, IVS1+31(G)7-8, IVS1+73-74ins(G), and 753A>G, were detected on the YWHAH, and three of them were novel. No significant associations were found between alcoholism and these polymorphisms or two additional polymorphisms on DRD4 exon III and DRD4 -521C/T. Conclusions: YWHAH and DRD4 do not appear to play a major role in the development of alcoholism.