No Association of the Structural Dopamine D2 Receptor (DRD2) Variant ³¹¹Cys with Alcoholism

Abstract

The human dopamine D2 receptor (DRD2) has been implied in the vulnerability for alcoholism and/or the modification of its severity. This is supported through animal experimental and pharmacological data. We analyzed the DRD2 311Ser/Cys polymorphism in 312 German alcoholics and 131 ethnically matched controls to investigate the association of genetic DRD2 variants with alcoholism or clinical characteristics of homogeneous subgroups of alcoholics. We observed no association between the 311Cys variant and alcoholism, and none of the clinical characteristics evaluated was significantly associated with 311Cys. The allele frequencies of the 311Cys variant were 0.026 and 0.031 in the alcoholics and controls, respectively. These are the highest reported 311Cys frequencies in Caucasians. The DRD2 TaqI A1/A2 restriction fragment length polymorphism was analyzed simultaneously in our samples. In most cases, the 311Cys allele is associated with the TaqI A2-allele. Data do not suggest a clinical relevance of the 311Cys variant in alcoholism. However, the relevance of this variant in other diseases or the existence of other DRD2 variants with altered receptor function or expression cannot be excluded.

Dopamine D2 Receptor Gene (DRD2) Is Associated With Alcoholism With Conduct Disorder

“…It seems that linkage disequilibrium would be highly improbable in any European population between this variant and other polymorphisms located 250kb away around the coding region of the gene (Jorde et al, 1994;Pakstis et al, 1997;Zhao et al, 1997). The other functional variation has been studied by several groups with equivocal results for alcoholism (Finckh et al, 1996). The Cys allele is infrequent-2-3% in Europeans (Gejman et al, 1994) and Japanese (Finckh et al, 1996) -and could not explain the reported association with alcoholism.…”

“…The other functional variation has been studied by several groups with equivocal results for alcoholism (Finckh et al, 1996). The Cys allele is infrequent-2-3% in Europeans (Gejman et al, 1994) and Japanese (Finckh et al, 1996) -and could not explain the reported association with alcoholism. Goldman et al (1997) have shown that this variant is much more common (about 16%) in at least one American Indian population but still shows no association or linkage with alcoholism.…”

DRD2 polymorphisms modulate reward and emotion processing, dopamine neurotransmission and openness to experience

“…Moreover, the functional significance and clinical relevance of these SNPs remains controversial (Finckh et al, 1996; Frank and Hutchison, 2009; Lucht et al, 2007). For this reason, it has been suggested that haplotype-based analyses, as a means of exploring a larger number of SNPs and their relationship with functional endophenotypes, may provide additional relevant information about the effects of DRD2 variation on brain function.…”

A large-scale meta-analysis of the association between the ANKK1/DRD2 Taq1A polymorphism and alcohol dependence

“…After filtration, 61 studies (refer to Supplementary Table S1) were considered eligible for the present meta-analysis. Among these 61 studies, 36 analyzed the association between the TaqA1 polymorphism and AD in the European population (Amadeo et al 1993; Amadeo et al 2000; Anghelescu et al 2001; Bau et al 2000; Berggren et al 2006; Bolos et al 1990; Comings et al 1991; Comings et al 1994; Cook et al 1992; Finckh et al 1996; Foley et al 2004; Freire et al 2006; Geijer et al 1994; Gelernter and Kranzler 1999; Gelernter et al 1991; Goldman et al 1992; Gorwood et al 2000a; Gorwood et al 2000b; Heinz et al 1996; Hietala et al 1997; Kasiakogia-Worlley et al 2011; Konishi et al 2004b; Kovanen et al 2010; Kraschewski et al 2009; Landgren et al 2011; Lawford et al 1997; Limosin et al 2002; Ovchinnikov et al 1999; Parsian et al 1991; Pastorelli et al 2001; Ponce et al 2008; Samochowiec et al 2008; Samochowiec et al 2000; Sander et al 1995; Sander et al 1999; Schellekens et al 2012); 18 analyzed the association between the TaqA1 polymorphism and AD in the Asian population (Arinami et al 1993; Bhaskar et al 2010; Chen et al 1996; Chen et al 1997; Huang et al 2007; Ishiguro et al 1998; Joe et al 2008; Kono et al 1997; Lee et al 1997; Lu et al 1996; Lu et al 2010; Lu et al 2001; Matsushita et al 2001; Namkoong et al 2008; Prasad et al 2010; Shaikh et al 2001; Wang et al 2007; Wu et al 2008); and seven analyzed the association between the TaqA1 polymorphism and AD in American Indians (Goldman et al 1993; Goldman et al 1997), a mix population (Blum et al 1991; Blum et al 1990; Sakai et al 2007), or other populations that were not stated (Neiswanger et al 1995; Noble et al 1994). …”