title: Leukemia inhibitory factor gene is associated with schizophrenia and working memory function.
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.
authors.affiliation: Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Okahisa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishihara
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kodama
authors.forename: Manabu
authors.initials: M
authors.lastname: Takaki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kotaka
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D053605:Leukemia Inhibitory Factor / Q000235:genetics*; D008297:Male; D008570:Memory, Short-Term / Q000502:physiology*; D008875:Middle Aged; D015999:Multivariate Analysis; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology*
chemical_list: D053605:Leukemia Inhibitory Factor