Leukemia inhibitory factor gene is associated with schizophrenia and working memory function
Leukemia inhibitory factor gene is associated with schizophrenia and working memory function
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白血病抑制因子基因与精神分裂症和工作记忆功能相关
DOI：
10.1016/j.pnpbp.2009.10.020
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Kuroda S
中科院分区：
文献类型：
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作者：
Okahisa Y;Ujike H;Kunugi H;Ishihara T;Kodama M;Takaki M;Kotaka T;Kuroda S
白血病抑制因子(LIF)是白介素6细胞因子家族的一员，调节神经元的表型，协调星形胶质细胞、少突胶质细胞、小胶质细胞和炎症细胞的反应。LIF基因位于22q12.1-q12.2，是精神分裂症的热点。对390例精神分裂症患者和410例年龄、性别匹配的对照组进行病例对照研究，检测LIF基因的3个多态(rs929271、rs737812和rs929273)。采用韦氏成人智力量表修订版、韦氏记忆量表修订版和威斯康星卡片分类测验(WCST)对355名健康志愿者进行了LIF危险基因对认知领域的影响。位于rs929271的LIF基因和由rs929271-rs737812组成的单倍型与精神分裂症显著相关。按精神分裂症亚型分层后，青春型与rs929271(等位基因，P=0.014)和单倍型(置换P=0.013)相关，而与偏执型无关。具有rs929271的T等位基因和T携带型(TT和TG)是青春型精神分裂症的危险因素，其OR值分别为1.38(95%CI：1.21~1.56)和1.54(95%CI：1.19~1.98)。携带T-携带者的受试者在WCST测试中的错误显著多于非携带者(P=0.04)。本研究提示LIF基因变异可能导致青春型精神分裂症的易感性和工作记忆功能的恶化。
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.