An Association Study Between Genetic Polymorphisms in Functional Regions of Five Genes and the Risk of Schizophrenia

J Mol Neurosci. 2016 Jul;59(3):366-75. doi: 10.1007/s12031-016-0751-6. Epub 2016 Apr 7.

Abstract

Schizophrenia is a severe mental disorder that is likely to be strongly determined by genetic factors. To identify markers of disks, large homolog 2 (DLG2), FAT atypical cadherin 3 (FAT3), kinectin1 (KTN1), deleted in colorectal carcinoma (DCC), and glycogen synthase kinase-3β (GSK3β) that contribute to the genetic susceptibility to schizophrenia, we systematically screened for polymorphisms in the functional regions of these genes. A total of 22 functional single-nucleotide polymorphisms (SNPs) in 940 Chinese subjects were genotyped using SNaPshot. The results first suggested that the allelic and genotypic frequencies of the DCC polymorphism rs2229080 were nominally associated with schizophrenia. The patients were significantly less likely to be CC homozygous (P = 0.005, odds ratio [OR] = 0.635, 95 % confidence interval [95 % CI] = 0.462-0.873), and the schizophrenia subjects exhibited lower frequency of the C allele (P = 0.024, OR = 0.811, 95 % CI = 0.676-0.972). Regarding GSK3β, there was a significant difference in genotype distribution of rs3755557 between schizophrenia and healthy control subjects (P = 0.009). The patients exhibited a significantly lower frequency of the T allele of rs3755557 (P = 0.002, OR = 0.654, 95 % CI = 0.498-0.860). Our results point to the polymorphisms of DCC and GSK3β as contributors to the genetic basis of individual differences in the susceptibility to schizophrenia.

Keywords: Chinese Han population; Deleted in colorectal carcinoma; Glycogen synthase kinase-3β; Schizophrenia; Single-nucleotide polymorphisms.

MeSH terms

  • Adult
  • Cadherins / genetics
  • Case-Control Studies
  • DCC Receptor
  • Epidermal Growth Factor / genetics
  • Female
  • Gene Frequency
  • Genotype
  • Glycogen Synthase Kinase 3 beta / genetics*
  • Guanylate Kinases / genetics
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Receptors, Cell Surface / genetics*
  • Schizophrenia / genetics*
  • Tumor Suppressor Proteins / genetics*

Substances

  • Cadherins
  • DCC Receptor
  • DCC protein, human
  • FAT3 protein, human
  • KTN1 protein, human
  • Membrane Proteins
  • Receptors, Cell Surface
  • Tumor Suppressor Proteins
  • Epidermal Growth Factor
  • Glycogen Synthase Kinase 3 beta
  • DLG2 protein, human
  • Guanylate Kinases