Significant association of DRD1 with nicotine dependence

Abstract

Epidemiologic studies have strongly implicated genetics in smoking behavior. Genes in the dopaminergic system, which mediates the reinforcing and dependence-producing properties of nicotine, are plausible candidates for roles in nicotine dependence (ND). In this study, we examined five single-nucleotide polymorphisms (SNPs) within or near the dopamine D(1) receptor gene (DRD1) for their association with ND, which was assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerström Test for ND (FTND). The samples were obtained from 2,037 participants representing 200 European American (EA) and 402 African American (AA) families. Although we found significant associations of SNPs rs265973, rs686, and rs4532 in the AA sample; of rs4532 in the EA sample; and of rs265975, rs686, and rs4532 in the pooled sample with various ND measures, only the association of rs686 in the AA sample and of rs686 and rs4532 in the pooled sample remained significant after correction for multiple testing. Haplotype-based association analysis revealed that haplotype C-T-A, formed by rs265973, rs265975, and rs686, was significantly associated with all three ND measures in both the AA and the pooled sample. Another haplotype, T-A-T, formed by rs265975, rs686, and rs4532, showed a significant association with FTND in the pooled sample. Furthermore, in a luciferase reporter assay, rs686, located in the 3' untranslated region, caused differential luciferase activities, indicating that rs686 is a functional polymorphism affecting expression of DRD1.

Association of polymorphisms in the BDNF, DRD1 and DRD3 genes with tobacco smoking in schizophrenia

“…Our observation that the DRD1 markers (rs4532, rs686) are associated with the number of cigarettes smoked per day is in agreement with the results of Huang et al, who have identified the same DRD1 markers as being strongly associated with nicotine addiction (Huang et al, 2008b). Furthermore, the DRD1 rs686 marker has been identified by Huang et al as a functional polymorphism, likely affecting the expression of this gene (Huang et al, 2008b).…”

“…To date, only one association study of DRD1 variants with nicotine addiction has been performed. Huang et al (2008b) found a significant association of two SNPs (rs686 and rs4532) with nicotine dependence, with the rs686 functional polymorphism likely affecting the expression of the dopamine D1 receptor.…”

“…We have genotyped 34 SNP variants spanning the DRD3 gene, as well as two SNPs at each end of the DRD1 gene, and six SNPs across the BDNF gene. The DRD1 SNPs selected were already shown to be significantly associated with nicotine addiction (Huang et al, 2008b).…”

Genome-wide association study of the five-factor model of personality in young Korean women

“…27 We also identified seven SNPs with Pp3.33 Â 10 À5 located near DRD1 on chromosome 5q35 (Figure 3). DRD1 has a role in behavior and psychiatric disorders, including schizophrenia, 28 autism, 29 attentiondeficit-hyperactivity disorder, 30 nicotine dependence 31 and alcohol dependence. 32 Among the top 30 SNPs for Neuroticism, three SNPs (rs265981, P ¼ 1.17 Â 10 À5 ; rs686, P ¼ 1.58 Â 10 À5 and rs4532, P ¼ 1.58 Â 10 À5 , Table 2 and Supplementary Table S1) were previously linked to psychiatric disorders.…”

Dopamine ADHD/OCD Theories: Is Glutamine Part of the Story?

“…Previous research had shown that the minor allele of rs4532 is more common in ADHD probands and predicted response and side-effects to drug treatment in schizophrenia, albeit associated with the DA antagonistic action of anti-psychotics rather than the agonistic action of stimulants (Bobb, Addington, Sidransky et al [15] ; Lai, Mo, Chen, Wang, Chen, Liao DL et al [16] ; Potkin, Basile, Jin, Masellis,Badri, Keator D et al [17] ). SNP rs4532 is located in the 5' UTR exon of the DRD1 gene and while its functional relevance is unclear, it may have affected DRD1 expression (Huang, Ma, Payne, Beuten, Dupont & Li [18] ).…”