Leukemia inhibitory factor gene is associated with schizophrenia and working memory function

Prog Neuropsychopharmacol Biol Psychiatry. 2010 Feb 1;34(1):172-6. doi: 10.1016/j.pnpbp.2009.10.020. Epub 2009 Oct 30.

Abstract

Leukemia inhibitory factor (LIF), a member of the interleukin-6 cytokine family, regulates the neuronal phenotype and coordinates astrocyte, oligodendrocyte, microglia, and inflammatory cell responses. The LIF gene is located on 22q12.1-q12.2, a hot spot for schizophrenia. Three polymorphisms of the LIF gene (rs929271, rs737812, and rs929273) were examined in a case-control association study of 390 patients with schizophrenia and 410 age- and sex-matched controls. Effects of a risk genotype of LIF on cognitive domains were evaluated by the Wechsler Adult Intelligence Scale-Revised, Wechsler Memory Scale-Revised, and Wisconsin Card Sorting Test (WCST) in 355 healthy volunteers. The LIF gene showed significant associations with schizophrenia at rs929271 and a haplotype consisting of rs929271-rs737812. After stratification by subtype of schizophrenia, the hebephrenic, but not paranoid, type was associated with the LIF gene at rs929271 (allele, P=0.014) and the haplotype (permutation P=0.013). Having the T-allele and T-carrier genotypes (TT and TG) of rs929271 were risks for hebephrenic schizophrenia, and the odds ratios were 1.38 (95% CI: 1.21-1.56) and 1.54 (95%CI: 1.19-1.98), respectively. Subjects with T-carrier genotypes made significantly more errors on the WCST compared with those without (P=0.04). The present study indicated that the LIF gene variant may produce susceptibility to hebephrenic schizophrenia and deterioration of working memory function.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Chi-Square Distribution
  • Female
  • Gene Frequency
  • Genome-Wide Association Study / methods
  • Genotype
  • Humans
  • Leukemia Inhibitory Factor / genetics*
  • Male
  • Memory, Short-Term / physiology*
  • Middle Aged
  • Multivariate Analysis
  • Neuropsychological Tests
  • Polymorphism, Single Nucleotide / genetics*
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology*

Substances

  • Leukemia Inhibitory Factor