title: Brain derived neurotrophic factor (BDNF) gene variants and Alzheimer's disease, affective disorders, posttraumatic stress disorder, schizophrenia, and substance dependence.
abstract: Genetic variation at the locus encoding the brain derived neurotrophic factor (BDNF) has been implicated in some neuropsychiatric disorders such as Alzheimer's disease (AD), affective disorders (AFDs), schizophrenia, and substance dependence. We therefore performed a mutation scan of the BDNF gene to identify novel gene variants and examined the association between BDNF variants and several neuropsychiatric phenotypes in European American (EA) subjects and controls. Using denaturing high performance liquid chromatography (dHPLC), we identified a novel variant (G-712A) in the putative promoter region. This variant and two previously reported BDNF SNPs (C270T and Val66Met) were genotyped in 295 patients with AD, 108 with AFDs, 96 with posttraumatic stress disorder (PTSD), 84 with schizophrenia, 327 with alcohol and/or drug dependence, and 250 normal control subjects. No association was found between these three BDNF gene variants and AD, AFDs, PTSD, or schizophrenia. However, there was a nominally higher frequency of the G-712A G-allele and the G/G genotype in subjects with substance dependence than in controls (Allele: chi(2) = 4.080, df = 1, P = 0.043; Genotype: chi(2) = 7.225, df = 2, P = 0.027). Although after correction for multiple testing, the findings are not considered significant (threshold P-value was set at 0.020 by the program SNPSpD), logistic regression analyses confirmed the modest association between SNP G-712A and substance dependence, when the sex and age of subjects were taken into consideration. The negative results for AFDs, PTSD, and schizophrenia could be due to the low statistical power. Further study with larger samples is warranted.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06516, USA.
authors.forename: Huiping
authors.initials: H
authors.lastname: Zhang
authors.forename: Fatih
authors.initials: F
authors.lastname: Ozbay
authors.forename: Jaakko
authors.initials: J
authors.lastname: Lappalainen
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: Christopher H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Charney
authors.forename: Lawrence H
authors.initials: LH
authors.lastname: Price
authors.forename: Steven
authors.initials: S
authors.lastname: Southwick
authors.forename: Bao-Zhu
authors.initials: BZ
authors.lastname: Yang
authors.forename: Ann
authors.initials: A
authors.lastname: Rasmussen
authors.forename: Joel
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics*; D013313:Stress Disorders, Post-Traumatic / Q000235:genetics*; D019966:Substance-Related Disorders / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor