BIOL PSYCHIATRY 285 1992;31:285-290 Lack of Association between an RFLP Near the D2 Dopamine Receptor Gene and Severe Alcoholism Eric Turner, John Ewing, Paul Shilling, Tom L. Smith, Michael Irwin, Marc Schuckit, and John R. Kelsoe Blum et al (1990) have recently examined a restriction fragment length polymorphism (RFLP) detected by Taql RFLP to the dopamine Dz receptor gene (DRD2) in deceased alcoholics and nonalcoholics, and reported an association between alcoholism and the AI allele. Subsequent studies, however, by other investigators have failed to confirm this. We have examined the DRD2 Taql RFLP in 47 living Caucasian males with severe alcoholism. All alcoholic subjects were thoroughly char~cterized by a structured inter- view, and met DSM-IlI-R criteria for alcohol dependence. Only 9147 (19%) (1990) of these alcoholics had the A1 allele compared to 14122 (64%) reported by Bium et al. This rate was not significantly different from the rates reported in control populations by Blum et al (1990), CEPH, or Bolos et al (1990), and differed only slightly from those reported by Grandy et al (1990). Alcoholics selected for severe medical cnmp!~cations also dis- played a similar rate. Our data do not support an association between alcoholism and the D2 dopamine receptor gene in this population. Introduction In response to studies demonstrating the probable importance of genetic factors in al- coholism (Schuckit 1985a; Tabakoff and Hoffman 1988a; Devor and Cloninger 1989), a number of laboratories are beginning to search for actual genes that might contribute to the risk for this disorder. One logical candidate is the dopamine D2 receptor, because dopamine pathways have been linked to neural reward mechanisms in addiction, although less strongly for alcohol than some other drugs (Tabakoff m~d Hoffman 1988b; Kornetsky et al 1988). The recent cloning of the rat D2 receptor ge~,~e(Bunzow et al 1988) has allowed localization of the human D2 receptor to the q22-q23 region of chromosome 11, and the identification of a Taql RFLP just beyond the 3' end of the transcribed region of the gene (Grandy et al 1989). The alleles were designated At and A2, corresponding to absence and presence of the Taql site, respectively, and allele frequencies of 23% and 77% were obtained in a population of 45 unrelated individuals (Grandy et al 1989; M. Litt, personal communication). Recently, Blum et al (1990) reported an association between the diagnosis of alcoholism and the presence of the At allele of the dopamine D2 receptor gene. This association was based on restriction fragment length polymorphisra (RFLP) ~alysis of genomic DNA From the Clinical Center for Research on Alcoholism, San Diego Veterans Affairs Medical Center, and the Department of Psychiatry M-003, University of California San Diego, La Jolla, CA 92093. Address reprint requests to John R. Keisoe, M.D., Departmentof Psychiatry, 0603, UC San Diego, La Jolla, CA 92093. Received February 4, 1991; revised May 10, 1991. © 1992 Society of Biological Psychiatry 0006-3223/92/$05.00