Association of β-Secretase Functional Polymorphism with Risk of Schizophrenia

Genet Test Mol Biomarkers. 2017 Apr;21(4):248-251. doi: 10.1089/gtmb.2016.0262. Epub 2017 Feb 21.

Abstract

Aim: 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.

Subjects and 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.

Conclusion: 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.

Keywords: BACE1; ERBB4; association; polymorphism; schizophrenia.

MeSH terms

  • Adult
  • Alleles
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism*
  • Aspartic Acid Endopeptidases / genetics*
  • Aspartic Acid Endopeptidases / metabolism*
  • Case-Control Studies
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Iran
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Receptor, ErbB-4 / genetics*
  • Receptor, ErbB-4 / metabolism
  • Risk Factors
  • Schizophrenia / etiology
  • Schizophrenia / genetics*
  • Signal Transduction

Substances

  • ERBB4 protein, human
  • Receptor, ErbB-4
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human