Heroin dependence is a debilitating psychiatric disorder with complex inheritance. Since the dopaminergic system has a key role in rewarding mechanism of the brain, which is directly or indirectly targeted by most drugs of abuse, we focus on the effects and interactions among dopaminergic gene variants. To study the potential association between allelic variants of dopamine D2 receptor (DRD2), ANKK1 (ankyrin repeat and kinase domain containing 1), dopamine D4 receptor (DRD4), catechol-O-methyl transferase (COMT) and dopamine transporter (SLC6A3) genes and heroin dependence in Hungarian patients. 303 heroin dependent subjects and 555 healthy controls were genotyped for 7 single nucleotide polymorphisms (SNPs) rs4680 of the COMT gene; rs1079597 and rs1800498 of the DRD2 gene; rs1800497 of the ANKK1 gene; rs1800955, rs936462 and rs747302 of the DRD4 gene. Four variable number of tandem repeats (VNTRs) were also genotyped: 120 bp duplication and 48 bp VNTR in exon 3 of DRD4 and 40 bp VNTR and intron 8 VNTR of SLC6A3. We also perform a multivariate analysis of associations using Bayesian networks in Bayesian multilevel analysis (BN-BMLA). In single marker analysis the TaqIA (rs1800497) and TaqIB (rs1079597) variants were associated with heroin dependence. Moreover, –521 C/T SNP (rs1800955) of the DRD4 gene showed nominal association with a possible protective effect of the C allele. After applying the Bonferroni correction TaqIB was still significant suggesting that the minor (A) allele of the TaqIB SNP is a risk component in the genetic background of heroin dependence. The findings of the additional multiple marker analysis are consistent with the results of the single marker analysis, but this method was able to reveal an indirect effect of a promoter polymorphism (rs936462) of the DRD4 gene and this effect is mediated through the –521 C/T (rs1800955) polymorphism in the promoter.

Background and aims: The primary aim of the present review was to summarize the findings of genetic studies conducted on problem and pathological gambling. Method: Literature searches were conducted using PubMed, Medline and the HuGE Navigator databases using the keywords ‘gambling’ and ‘genetic*’. Results: The literature searches identified 21 empirical studies that had analyzed data from eight independent samples. Empirical research utilizing twin data accounted for eight of the studies, while gene association data were presented in 13 studies (including one genome wide-association study [GWAS] study). Twin studies emphasized the significant role of genetic and individual environmental factors in problem and pathological gambling. Gene association studies primarily reported the involvement of the dopaminergic and serotonergic systems. Discussion: Despite the relatively low number of genetic studies, the data clearly indicated the genetic vulnerability of problem and pathological gambling. Studies to date have mainly investigated and verified the role of factors reported to be important in other types of addiction, and it is suggested that pathological gambling should be included as a subtype of ‘Reward Deficiency Syndrome’ (RDS). It is concluded that future research should attempt to identify possible gambling specific susceptibility factors.