title: Significant association of BDNF haplotypes in European-American male smokers but not in European-American female or African-American smokers.
abstract: Brain-derived neurotrophic factor (BDNF) influences dopamine and serotonin neurotransmission in the brain, both of which are involved in the reward system of addiction. The BDNF gene is located in a genomic region on chromosome 11p where we and others have found 'significant' linkage to nicotine dependence (ND). We tested the potential role of variants within BDNF in vulnerability to ND, which was assessed by Smoking Quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerström Test for ND (FTND). Six single nucleotide polymorphisms (SNPs) in BDNF were analyzed in an extensively phenotyped cohort of 602 nuclear families with smokers and non-smokers of African-American (AA) or European-American (EA) ancestry. Individual SNP analysis revealed that two SNPs in the pooled male and three SNPs in the EA male samples were significantly associated with at least one adjusted ND measure. However, none of these associations remained significant after correction for multiple testing. Haplotype analysis of rs6484320-rs988748-rs2030324-rs7934165 revealed that a major T-C-T-G haplotype was significantly associated, even after Bonferroni correction, with the three ND measures in the pooled and EA male samples (maximum Z = 3.00, P = 0.002 and maximum Z = 3.13, P = 0.0009 for SQ, respectively). No significant association of a major haplotype with ND was found in the AA or EA female smokers. The significant association of BDNF variants with ND implies that this gene plays a role in the etiology of ND in EAs and that its involvement is gender specific. BDNF may warrant further investigation in ND.
authors.affiliation: Program in Genomics and Bioinformatics on Drug Addiction, Department of Psychiatry, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
authors.forename: Joke
authors.initials: J
authors.lastname: Beuten
authors.forename: Jennie Z
authors.initials: JZ
authors.lastname: Ma
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Payne
authors.forename: Randolph T
authors.initials: RT
authors.lastname: Dupont
authors.forename: Paulina
authors.initials: P
authors.lastname: Quezada
authors.forename: Weihua
authors.initials: W
authors.lastname: Huang
authors.forename: Karen M
authors.initials: KM
authors.lastname: Crews
authors.forename: Ming D
authors.initials: MD
authors.lastname: Li
mesh_terms: D000328:Adult; D001741:Black or African American; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics; D012907:Smoking / Q000235:genetics* / Q000503:physiopathology; D014029:Tobacco Use Disorder / Q000235:genetics* / Q000503:physiopathology; D044465:White People
chemical_list: D019208:Brain-Derived Neurotrophic Factor