PMID- 23280964
OWN - NLM
STAT- MEDLINE
DCOM- 20130918
LR  - 20211108
IS  - 1552-485X (Electronic)
IS  - 1552-4841 (Linking)
VI  - 162B
IP  - 2
DP  - 2013 Mar
TI  - Refinement of chromosome 3p22.3 region and identification of a susceptibility 
      gene for bipolar affective disorder.
PG  - 163-8
LID - 10.1002/ajmg.b.32127 [doi]
AB  - Genome-wide association studies and meta-analysis, as well as our own previous 
      family-based association results, have pointed to chromosome (ch) 3p22.3 and 
      3p21.1 as candidate regions to contain a susceptibility gene for bipolar 
      affective disorder (BPAD). In the present study, we further refined the region of 
      interest on ch 3p22.3. We genotyped 94 SNPs within the candidate region in 74 
      families and performed family-based association analysis using a transmission 
      disequilibrium test. One single SNP (rs166508) was associated with the BPAD 
      phenotype (P = 0.0187). This SNP is located within intron 15 of the integrin 
      alpha 9 (ITGA9) gene. ITGA9 encodes the alpha9 subunit of the alpha9beta1 integrin, a 
      membrane glycoprotein receptor for neurotrophins, such as nerve growth factor 
      (NGF) and brain-derived neurotrophic factor (BDNF). Quantification of ITGA9 
      transcripts in the peripheral blood of patients with BPAD and controls showed an 
      upregulation of ITGA9 (Kruskal-Wallis P = 0.0339) in patients with the 
      disease-associated genotype (rs166508*A/A), compared to those with rs166508*G/G 
      and rs166508*G/A genotypes. Sequencing of the ITGA9 cDNA revealed a sequence 
      variant (r.1689_1839del) in rs166508*A carriers, which leads to loss of the 
      entire exon 16. In silico analysis revealed that the deleted region contains 
      three putative microRNA binding sites, which may be involved in the negative 
      regulation of ITGA9. In conclusion, our results confirm previous evidence 
      pointing to a candidate region for BPAD on ch 3p.22.3. In addition, we suggest a 
      molecular substrate that could explain the increase of ITGA9 mRNA levels in 
      probands with BPAD, proposing a new mechanism that could be involved in the 
      genetic susceptibility to the disease.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Secolin, Rodrigo
AU  - Secolin R
AD  - Department of Medical Genetics, University of Campinas-UNICAMP, Campinas, SP, 
      Brazil.
FAU - Banzato, Claudio E M
AU  - Banzato CE
FAU - Mella, Lucas F B
AU  - Mella LF
FAU - Santos, Marilza L
AU  - Santos ML
FAU - Dalgalarrondo, Paulo
AU  - Dalgalarrondo P
FAU - Lopes-Cendes, Iscia
AU  - Lopes-Cendes I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121231
PL  - United States
TA  - Am J Med Genet B Neuropsychiatr Genet
JT  - American journal of medical genetics. Part B, Neuropsychiatric genetics : the 
      official publication of the International Society of Psychiatric Genetics
JID - 101235742
RN  - 0 (DNA, Complementary)
RN  - 0 (ITGA9 protein, human)
RN  - 0 (Integrins)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Base Sequence
MH  - Bipolar Disorder/*genetics
MH  - Chromosomes, Human, Pair 3/*genetics
MH  - DNA, Complementary/genetics
MH  - Gene Expression Regulation
MH  - Gene Frequency/genetics
MH  - *Genetic Association Studies
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Integrins/genetics/metabolism
MH  - Molecular Sequence Data
MH  - Polymorphism, Single Nucleotide/genetics
MH  - RNA, Messenger/genetics/metabolism
EDAT- 2013/01/03 06:00
MHDA- 2013/09/21 06:00
CRDT- 2013/01/03 06:00
PHST- 2011/10/28 00:00 [received]
PHST- 2012/12/07 00:00 [accepted]
PHST- 2013/01/03 06:00 [entrez]
PHST- 2013/01/03 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
AID - 10.1002/ajmg.b.32127 [doi]
PST - ppublish
SO  - Am J Med Genet B Neuropsychiatr Genet. 2013 Mar;162B(2):163-8. doi: 
      10.1002/ajmg.b.32127. Epub 2012 Dec 31.