title: A DRD2 and ANKK1 haplotype is associated with nicotine dependence.
abstract: To test the importance of the dopamine D2 receptor (DRD2) region in nicotine dependence, 150 smokers and 228 controls were genotyped for the DRD2 C957T, -141delC and ANKK1 TaqIA polymorphisms (rs6277, rs1799732 and rs1800497, respectively). The -141delC SNP did not show any association but both the C957T and TaqIA SNPs showed association at the allele, genotype, haplotype and combined genotype levels. The 957C/TaqI A1 haplotype was more than 3.5 times as likely to be associated with nicotine dependence compared with the 957T/TaqI A1 haplotype (P=0.003). Analysis of the combined genotypes of both SNPs revealed that individuals who were homozygous for the 957C-allele (CC) and had either one or two copies of the TaqI A1-allele were 3.3 times as likely to have nicotine dependence compared to all other genotype combinations (P=0.0003) and that these genotypes accounted for approximately 13% of the susceptibility to nicotine addiction in our population. Our findings suggest that the DRD2 C957T polymorphism and the ANKK1 TaqIA polymorphism are key contributors to the genetic susceptibility to nicotine dependence.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. j.voisey@qut.edu.au
authors.forename: Joanne
authors.initials: J
authors.lastname: Voisey
authors.forename: Christopher Dean
authors.initials: CD
authors.lastname: Swagell
authors.forename: Ian Paul
authors.initials: IP
authors.lastname: Hughes
authors.forename: Angela
authors.initials: A
authors.lastname: van Daal
authors.forename: Ernest Pascal
authors.initials: EP
authors.lastname: Noble
authors.forename: Bruce Robert
authors.initials: BR
authors.lastname: Lawford
authors.forename: Ross McDonald
authors.initials: RM
authors.lastname: Young
authors.forename: Charles Phillip
authors.initials: CP
authors.lastname: Morris
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D014029:Tobacco Use Disorder / Q000235:genetics*; D055815:Young Adult
chemical_list: D017448:Receptors, Dopamine D2; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases