title: Polymorphisms of BDNF gene and autism spectrum disorders: family based association study with korean trios.
abstract: OBJECTIVE
  Autism spectrum disorders (ASDs) are a group of early childhood-onset neurodevelopmental disorders characterized by deficits in social interaction and language skills, and repetitive behaviors. Brain-derived neurotrophic factor (BDNF) plays a critical role in the differentiation of normal neuronal cells during embryonic and postnatal neuronal development through its neurotrophic effects.
  
  
  METHODS
  In this study, we performed a family-based association test (FBAT) between single nucleotide polymorphisms (SNPs; rs6265, rs11030101, rs7103411, and rs7103873) or haplotypes in the BDNF gene and affection status or several quantitative traits characterized by ADI-R with151 Korean trios, including a child diagnosed as ASDs.
  
  
  RESULTS
  While no significant association was found between SNPs or haplotypes and the ASDs disease status, a quantitative transmission disequilibrium test (QTDT) by using quantitative traits identified associations of the SNPs (rs6265 and rs11030101) with a domain score for "Restricted, Repetitive and Stereotyped patterns of behavior" (C domain), especially at the subdomain scores for "encompassing preoccupation or circumscribed pattern of interest" (C1) (rs6265A allele, dominant model, p-value=0.019; rs11030101 A allele, additive model, p-value=0.015) and "preoccupations with part of objects or non-functional elements of material" (C4) (rs11030101 A allele, additive model, p-value=0.015) within the ADI-R diagnostic algorithm. In addition, significant associations were also identified between the haplotypes and these quantitative traits (C1, p-value=0.016; C4, p-value=0.012).
  
  
  CONCLUSIONS
  We conclude that BDNF gene polymorphisms have a possible role in the pathogenesis of ASDs.
authors.affiliation: Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Hee Jeong
authors.initials: HJ
authors.lastname: Yoo
authors.affiliation: Department of Pharmacology, Chungnam National University College of Pharmacy, Daejeon, Republic of Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, Gachon University of Medicine and Science, Incheon, Republic of Korea.
authors.forename: In Hee
authors.initials: IH
authors.lastname: Cho
authors.affiliation: Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Republic of Korea.
authors.forename: Mira
authors.initials: M
authors.lastname: Park
authors.affiliation: Department of Pharmacology, School of Medicine, Eulji University, Daejeon, Republic of Korea.
authors.forename: Soon Ae
authors.initials: SA
authors.lastname: Kim
keywords: Autism spectrum disorders; Brain derived neurotropic factor; Family based association study; Quantitative transmission disequilibrium test
references.citation: Biochem Biophys Res Commun. 2007 Apr 27;356(1):200-6
references.pmid: 17349978
references.citation: PLoS One. 2013;8(1):e53596
references.pmid: 23320097
references.citation: J Biomed Nanotechnol. 2009 Oct;5(5):542-50
references.pmid: 20201430
references.citation: Nature. 1996 May 2;381(6577):71-5
references.pmid: 8609991
references.citation: Int J Dev Neurosci. 2007 Oct;25(6):367-72
references.pmid: 17804189
references.citation: Dialogues Clin Neurosci. 2009;11(1):35-43
references.pmid: 19432386
references.citation: Bioinformatics. 2005 Jan 15;21(2):263-5
references.pmid: 15297300
references.citation: Autism Res. 2008 Feb;1(1):4-17
references.pmid: 19360646
references.citation: J Neurodev Disord. 2009 Sep;1(3):215-23
references.pmid: 21547716
references.citation: Hum Genet. 2011 Jul;130(1):123-48
references.pmid: 21701786
references.citation: Psychol Med. 1995 Jan;25(1):63-77
references.pmid: 7792363
references.citation: Nature. 2002 Oct 17;419(6908):687-93
references.pmid: 12384689
references.citation: Dev Neurobiol. 2010 Apr;70(5):304-22
references.pmid: 20186705
references.citation: Med Hypotheses. 2005;65(1):79-82
references.pmid: 15893122
references.citation: Brain Dev. 2004 Aug;26(5):292-5
references.pmid: 15165668
references.citation: J Biol Chem. 2002 Sep 6;277(36):32692-6
references.pmid: 12082117
references.citation: J Autism Dev Disord. 2009 Nov;39(11):1542-51
references.pmid: 19582565
references.citation: J Physiol. 2006 Aug 1;574(Pt 3):787-803
references.pmid: 16709633
references.citation: Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13069-74
references.pmid: 14557544
references.citation: Ann Neurol. 2001 May;49(5):597-606
references.pmid: 11357950
references.citation: Neurosci Res. 2012 Aug;73(4):333-6
references.pmid: 22698779
references.citation: Am J Med Genet A. 2011 Jun;155A(6):1272-80
references.pmid: 21567907
references.citation: J Neurosci. 2006 Nov 1;26(44):11487-500
references.pmid: 17079678
references.citation: Behav Brain Res. 2013 Aug 15;251:35-40
references.pmid: 23270976
references.citation: Ann Neurol. 1994;35 Suppl:S9-12
references.pmid: 8185304
references.citation: J Autism Dev Disord. 1994 Oct;24(5):659-85
references.pmid: 7814313
references.citation: Cortex. 2013 Nov-Dec;49(10):2700-10
references.pmid: 23517654
references.citation: Brain Res Brain Res Rev. 2002 Jun;39(1):29-54
references.pmid: 12086707
references.citation: Genet Epidemiol. 2001;21 Suppl 1:S403-8
references.pmid: 11793708
references.citation: Annu Rev Neurosci. 2001;24:677-736
references.pmid: 11520916
references.citation: Nat Genet. 2007 Mar;39(3):319-28
references.pmid: 17322880