title: Brain-derived neurotrophic factor gene polymorphisms: influence on treatment response phenotypes of major depressive disorder.
abstract: Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor family of neurotrophins, has pivotal roles in neuronal survival, proliferation, and synaptic plasticity in the brain. Both clinical and pharmacological studies have implicated the common single nucleotide polymorphism (SNP) at position 196, Val66Met in the pathophysiology of major depressive disorder (MDD), and antidepressant response. However, inconsistent results were found between Val66Met (rs6265) polymorphism and treatment response phenotypes in genetic association studies. The functional Val66Met polymorphism and seven other tagging SNP markers selected to capture the major allelic variations across BDNF locus were analyzed in depressed patients, treated with antidepressants, and 76 control patients. Two hundred and six patients with Diagnostic and Statistical Manual of Mental Disorders-IV MDD were recruited for this study and genotyped for eight BDNF tagging SNPs (rs11030096, rs925946, rs10501087,rs6265, rs12273363, rs908867, rs1491850, and rs1491851)to investigate the functional impact of genotypes/haplotypes in the susceptibility of depression and on treatment response. None of the eight SNPs, including the rs6265, were significantly associated with MDD after permutation correction. However, we found an association for rs10501087, rs6265 with nonresponse to antidepressant treatment (corrected permutation P:0.03599; 0.0399 and power: 0.1420; 0.1492, respectively).Analysis of each two-marker, three-marker, and four-marker sliding window haplotypes showed significance in haplotype combinations. Especially rs10501087 (C), rs6265 (A), and rs149,1850 (C) together or with the other SNP haplotypes showed a similar pattern in all treatment response phenotypes. Despite the limited power of analysis, our results suggest that these three SNPs may play a role in antidepressant treatment response phenotypes in MDD.
authors.affiliation: Laboratoire de Neurologie Expérimentale, Université Libre de Bruxelles, Laboratoire de Neurologie Expérimentale, Campus Hôpital Erasme C2.124, 808 Route de Lennik, 1070 Bruxelles, Belgium. naygunko@ulb.ac.be
authors.forename: Neslihan Aygun
authors.initials: NA
authors.lastname: Kocabas
authors.forename: Irina
authors.initials: I
authors.lastname: Antonijevic
authors.forename: Carole
authors.initials: C
authors.lastname: Faghel
authors.forename: Carlos
authors.initials: C
authors.lastname: Forray
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.forename: Yves
authors.initials: Y
authors.lastname: Lecrubier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Linotte
authors.forename: Isabelle
authors.initials: I
authors.lastname: Massat
authors.forename: Julien
authors.initials: J
authors.lastname: Mendlewicz
authors.forename: Magali
authors.initials: M
authors.lastname: Noro
authors.forename: Stuart
authors.initials: S
authors.lastname: Montgomery
authors.forename: Pierre
authors.initials: P
authors.lastname: Oswald
authors.forename: Lenore
authors.initials: L
authors.lastname: Snyder
authors.forename: Joseph
authors.initials: J
authors.lastname: Zohar
authors.forename: Daniel
authors.initials: D
authors.lastname: Souery
mesh_terms: D000483:Alleles; D000928:Antidepressive Agents / Q000627:therapeutic use*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012074:Remission Induction; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor