PMID- 19414708 OWN - NLM STAT- MEDLINE DCOM- 20090518 LR - 20221207 IS - 1538-3636 (Electronic) IS - 0003-990X (Print) IS - 0003-990X (Linking) VI - 66 IP - 5 DP - 2009 May TI - Novel sequence variations in the brain-derived neurotrophic factor gene and association with major depression and antidepressant treatment response. PG - 488-97 LID - 10.1001/archgenpsychiatry.2009.38 [doi] AB - CONTEXT: Variations in the brain-derived neurotrophic factor gene (BDNF) have been associated with psychiatric disorders. Deep sequencing of the BDNF gene may identify new variations and bring further insight into psychiatric genetics. OBJECTIVE: To better characterize sequence variability in the BDNF gene by resequencing a genomic DNA region of 22 kilobases that contained all BDNF exons and their flanking regions. DESIGN: Case-control study. SETTING: University of California, Los Angeles, and University of Miami. PARTICIPANTS: Two hundred sixty-four controls and 272 Mexican Americans with major depressive disorder (MDD) from Los Angeles who were assessed by the same bilingual clinical research team. MAIN OUTCOME MEASURES: Identification of novel genetic polymorphisms in the BDNF gene and assessment of their frequencies and associations with MDD or antidepressant response. RESULTS: We identified 83 novel single-nucleotide polymorphisms (SNPs): 30 in untranslated regions, 4 in coding sequences, 37 in introns, and 12 in upstream regions; 3 of 4 rare novel coding SNPs were nonsynonymous. Association analyses of patients with MDD and controls showed that 6 SNPs were associated with MDD (rs12273539, rs11030103, rs6265, rs28722151, rs41282918, and rs11030101) and 2 haplotypes in different blocks (one including Val66, another near exon VIIIh) were significantly associated with MDD. One recently reported 5' untranslated region SNP, rs61888800, was associated with antidepressant response after adjusting for age, sex, medication, and baseline score on the 21-item Hamilton Depression Rating Scale. CONCLUSIONS: Our data support the concept that extensive resequencing of key candidate genes can lead to the discovery of substantial numbers of new variants. Further studies using larger independent samples are needed to confirm the association of the rs61888800 SNP with antidepressant response. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00265291. FAU - Licinio, Julio AU - Licinio J AD - Center on Pharmacogenomics, Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, Florida 33136, USA. licinio@miami.edu FAU - Dong, Chuanhui AU - Dong C FAU - Wong, Ma-Li AU - Wong ML LA - eng SI - ClinicalTrials.gov/NCT00265291 GR - M01 RR000865/RR/NCRR NIH HHS/United States GR - MH062777/MH/NIMH NIH HHS/United States GR - DK063240/DK/NIDDK NIH HHS/United States GR - RR017365/RR/NCRR NIH HHS/United States GR - R03 HG002500/HG/NHGRI NIH HHS/United States GR - K24 RR017365/RR/NCRR NIH HHS/United States GR - RR16996/RR/NCRR NIH HHS/United States GR - WT_/Wellcome Trust/United Kingdom GR - HG002500/HG/NHGRI NIH HHS/United States GR - RR000865/RR/NCRR NIH HHS/United States GR - R01 DK063240/DK/NIDDK NIH HHS/United States GR - U01 GM061394/GM/NIGMS NIH HHS/United States GR - K24 RR016996/RR/NCRR NIH HHS/United States GR - R21 MH062777/MH/NIMH NIH HHS/United States GR - GM61394/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PL - United States TA - Arch Gen Psychiatry JT - Archives of general psychiatry JID - 0372435 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Genetic Markers) RN - 0 (Untranslated Regions) RN - 01K63SUP8D (Fluoxetine) RN - TG537D343B (Desipramine) SB - IM MH - Adult MH - Aged MH - *Alleles MH - Antidepressive Agents/therapeutic use MH - Brain-Derived Neurotrophic Factor/*genetics MH - Case-Control Studies MH - Depressive Disorder, Major/diagnosis/drug therapy/*genetics MH - Desipramine/therapeutic use MH - Double-Blind Method MH - Female MH - Fluoxetine/therapeutic use MH - Gene Frequency/genetics MH - Genetic Markers/genetics MH - Genetic Variation/*genetics MH - Haplotypes MH - Humans MH - Introns/genetics MH - Los Angeles MH - Male MH - Mexican Americans/*genetics MH - Middle Aged MH - Open Reading Frames/genetics MH - Pharmacogenetics MH - Polymorphism, Single Nucleotide/*genetics MH - *Sequence Analysis, DNA MH - Treatment Outcome MH - Untranslated Regions MH - White People/genetics MH - Young Adult PMC - PMC4272010 MID - NIHMS645315 EDAT- 2009/05/06 09:00 MHDA- 2009/05/19 09:00 PMCR- 2014/12/19 CRDT- 2009/05/06 09:00 PHST- 2009/05/06 09:00 [entrez] PHST- 2009/05/06 09:00 [pubmed] PHST- 2009/05/19 09:00 [medline] PHST- 2014/12/19 00:00 [pmc-release] AID - 66/5/488 [pii] AID - 10.1001/archgenpsychiatry.2009.38 [doi] PST - ppublish SO - Arch Gen Psychiatry. 2009 May;66(5):488-97. doi: 10.1001/archgenpsychiatry.2009.38.