Significant association of DRD1 with nicotine dependence.
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.
Huang
Weihua
W
Department of Psychiatry and Neurobehavioral Sciences, Section of Neurobiology, University of Virginia, 1670 Discovery Drive, Suite 125, Charlottesville, VA 22911, USA.
Ma
Jennie Z
JZ
Payne
Thomas J
TJ
Beuten
Joke
J
Dupont
Randolph T
RT
Li
Ming D
MD
D020413:3' Untranslated Regions / Q000235:genetics; D001741:Black or African American; D015331:Cohort Studies; D017931:DNA Primers / Q000235:genetics; D005190:Family; D005260:Female; D008040:Genetic Linkage; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008297:Male; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017447:Receptors, Dopamine D1 / Q000235:genetics*; D012907:Smoking; D014029:Tobacco Use Disorder / Q000235:genetics*; D014407:Tumor Cells, Cultured; D044465:White People
D020413:3' Untranslated Regions; D017931:DNA Primers; D017447:Receptors, Dopamine D1; D008156:Luciferases