title: Association of β-Secretase Functional Polymorphism with Risk of Schizophrenia.
abstract: OBJECTIVE
  The NRG1-ERBB4 neurotransmitter signaling pathway plays a key role in the pathogenesis of schizophrenia (SZ). The intronic single-nucleotide polymorphism rs707284 in ERBB4 links to PI3K-AKT suppression in SZ. Another protein indirectly affecting NRG1-ERBB4 signaling is β-secretase, which is encoded by the BACE1 gene, and activates NRG1 by proteolytic cleavage. In this study, we aimed to investigate the association of ERBB4 rs707284 and BACE1 rs490460 with the risk of SZ in an Iranian population.
  
  
  METHODS
  A total of 973 subjects, including 480 SZ patients and 493 healthy controls, matched by ethnicity, age, and gender, were recruited in a case-control study. Genomic DNA was extracted from peripheral blood of all subjects and genotyping of rs707284 and rs490460 was performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and tetra-primer amplification refractory mutation system (tetra-ARMS) PCR genotyping assays, respectively.
  
  
  RESULTS
  A significant association was observed between the rs490460 T allele and SZ (p = 0.0002, odds ratio 0.69, 95% confidence interval 0.57-0.84). There was no association between the risk of SZ and rs707284.
  
  
  CONCLUSIONS
  Our data indicate that rs490460 is associated with the risk of SZ. In silico analysis indicates that rs490460 may be a potential splicing site, which affects protein structure. Replication studies are needed to confirm our data.
authors.affiliation: 1 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran .
authors.forename: Simin
authors.initials: S
authors.lastname: Rahimi-Aliabadi
authors.affiliation: 2 Cellular and Molecular Biology Research Center, Babol University of Medical Sciences , Babol, Iran .
authors.forename: Neda
authors.initials: N
authors.lastname: Shahmohammadibeni
authors.affiliation: 3 Noncommunicable Diseases Research Center, Fasa University of Medical Sciences , Fasa, Iran .
authors.forename: Javad
authors.initials: J
authors.lastname: Jamshidi
authors.affiliation: 4 Department of Neurology, Ganjavian Hospital, Dezful University of Medical Sciences , Dezful, Iran .
authors.forename: Ehsan Esmaili
authors.initials: EE
authors.lastname: Shandiz
authors.affiliation: 1 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran .
authors.forename: Reza
authors.initials: R
authors.lastname: Mirfakhraie
authors.affiliation: 5 Iranian Research Center on Aging, University of Social Welfare and Rehabilitation Sciences , Tehran, Iran .
authors.forename: Mina
authors.initials: M
authors.lastname: Ohadi
authors.affiliation: 6 The Charitable Institute for Protecting of Social Victims (Saray-e-Ehsan) , Tehran, Iran .
authors.forename: Farhad Ramezani
authors.initials: FR
authors.lastname: Nejad
authors.affiliation: 6 The Charitable Institute for Protecting of Social Victims (Saray-e-Ehsan) , Tehran, Iran .
authors.forename: Nader
authors.initials: N
authors.lastname: Mansoori
authors.affiliation: 1 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran .
authors.forename: Mohammad
authors.initials: M
authors.lastname: Taheri
authors.affiliation: 7 Department of Psychiatry, Emam Hossien Hospital, Shahid Beheshti University of Medical Sciences , Tehran, Iran .
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Gholipour
authors.affiliation: 8 Social Determinants of Health Research Center, Health Research Institute, Babol University of Medical Sciences , Babol, Iran .
authors.forename: Susan
authors.initials: S
authors.lastname: Moudi
authors.affiliation: 9 Department of Psychiatry, Faculty of Medicine, Babol University of Medical Sciences , Babol, Iran .
authors.forename: Gouya
authors.initials: G
authors.lastname: Tayebi
authors.affiliation: 10 Zareh Hospital, Mazandaran University of Medical Sciences , Sari, Iran .
authors.forename: Shahram
authors.initials: S
authors.lastname: Divsalar
authors.affiliation: 1 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran .
authors.forename: Hossein
authors.initials: H
authors.lastname: Darvish
authors.affiliation: 1 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences , Tehran, Iran .
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Movafagh
mesh_terms: D000328:Adult; D000483:Alleles; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000235:genetics* / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007492:Iran; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D066247:Receptor, ErbB-4 / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D012559:Schizophrenia / Q000209:etiology / Q000235:genetics*; D015398:Signal Transduction
chemical_list: C587689:ERBB4 protein, human; D066247:Receptor, ErbB-4; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: BACE1; ERBB4; association; polymorphism; schizophrenia