ABSTRACT
Development of an addiction is conditioned by many factors. The dopaminergic system has been shown to be the key element in this process. In this paper, we analyzed the influence of dopamine receptor 2 polymorphism rs1076560 in two groups-polysubstance-dependent male patients (n = 299) and the controls matched for age (n = 301). In both groups, we applied the same questionnaires for testing-Mini-international neuropsychiatric interview, the NEO Five-Factor Inventory, and the State-Trait Anxiety Inventory. The real-time PCR method was used for genotyping. When we compared the controls with the case group subjects, we observed significantly higher scores in the second group on both the state and trait scales of anxiety, as well as on the Neuroticism and Openness scales of the NEO-FFI; and lower scores on the scales of Extraversion and Agreeability of the NEO-FFI. The model 2×3 factorial ANOVA of the addicted subjects and controls was performed, and the DRD2 rs1076560 variant interaction was found for the anxiety state and trait scales, and for the NEO-FFI Neuroticism scale. The observed associations allow noticing that analysis of psychological factors in combination with genetic data opens new possibilities in addiction research.
ABSTRACT
OBJECTIVES: The aim of the study was to determine relationships between the selected DRD2 gene polymorphisms and drug addiction. METHODS: One hundred drug abusers undergoing treatment were recruited from the inpatient psychiatric centers in Poland. All participants were screened by means of the clinical interview SSAGA to describe the clinical picture. In the second part of the study, participants were examined using psychometric tools assessing selected psychopathological features. After that, blood samples were collected for a DNA isolation. The following DRD2 single nucleotide polymorphisms (SNPs) of the dopamine gene were genotyped: rs1800498 polymorphism of DRD2 gene (NC_000011.10:g.113420866G>A, GRCh38.p7); rs1079597 polymorphism of DRD2 gene (NC_000011.10:g.113425564C>T, GRCh38.p7); rs1076560 polymorphism of DRD2 gene (NC_000011.10:g.113412966C>A, GRCh38.p7). RESULTS: The rs1800498 polymorphism has shown an association with drug abuse in which a higher frequency of the allelic T form was observed in the whole group of patients and selected subgroups with concomitant opiates or cannabis abuse history when compared with the controls. CONCLUSIONS: In the presented study, one of selected polymorphisms of DRD2 gene, revealed to be correlated with substance use disorder (at the limit of statistical significance), which could suggest its impact on dependence endophenotype. The presented research was a pilot study, so it requires replication on a larger group of patients to verify and confirm obtained outcomes.
Subject(s)
Drug Users , Genotype , Receptors, Dopamine D2/genetics , Substance-Related Disorders/genetics , Adult , Alleles , Case-Control Studies , Disease Susceptibility , Female , Genetic Predisposition to Disease , Humans , Male , Poland , Polymorphism, Single Nucleotide , Young AdultABSTRACT
The paper focuses on such candidate gene polymorphisms that alter alcoholism-related intermediate phenotypes including: dopaminergic system polymorphic variants (DRD2 -141C Ins/Del in promoter region, exon 8 and DRD2 TaqI A and DAT 40bp VNTR genes polymorphisms) that cause predisposition to severe alcoholism (haplotype Ins/G/A2); COMT Val158Met gene polymorphism related to differences in executive cognitive function and 5-HTT gene promoter polymorphism, which alters stress response and affects anxiety and dysphoria. The transmission disequilibrium test (TDT) was used in the study. One hundred Polish families with alcohol dependence were recruited. The control subjects for the case-control study were 196 ethnically and gender matched healthy individuals. It was found that DRD2 TaqIA and DAT gene polymorphisms contained statistically significant differences in allele transmission. In the homogenous subgroups of patients with early onset and with withdrawal complications a statistically significant preferential A2 allele transmission was found in DRD2 TaqIA gene polymorphism. The alleles and genotypes distribution of the investigated polymorphisms did not differ significantly between the alcoholics and the controls in the case-control study. The results confirmed the fact that the candidate genes (DRD2 and DAT) are partially responsible for the development of alcohol dependence. The results are also in agreement with the hypothesis that there are various subtypes of alcohol dependence, which differ depending on their genetic background. Meanwhile, the currently available pharmacological therapies for alcoholism treatment are effective in some alcoholics but not for all of them. Some progress has been made in elucidating pharmacogenomic responses to drugs, particularly in the context of Clonninger and Lesch typology classification system for alcoholics.
