Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan.
Behav Brain Funct. 2011 Aug 16;7:35. doi: 10.1186/1744-9081-7-35.
Several lines of evidence have implicated the pro-inflammatory cytokine interleukin-1beta (IL-1β) in the etiology of schizophrenia. Although a number of genetic association studies have been reported, very few have systematically examined gene-wide tagging polymorphisms.
A total of 533 patients with schizophrenia (302 males: mean age ± standard deviation 43.4 ± 13.0 years; 233 females; mean age 44.8 ± 15.3 years) and 1136 healthy controls (388 males: mean age 44.6 ± 17.3 years; 748 females; 46.3 ± 15.6 years) were recruited for this study. All subjects were biologically unrelated Japanese individuals. Five tagging polymorphisms of IL-1β gene (rs2853550, rs1143634, rs1143633, rs1143630, rs16944) were examined for association with schizophrenia.
Significant difference in allele distribution was found between patients with schizophrenia and controls for rs1143633 (P = 0.0089). When the analysis was performed separately in each gender, significant difference between patients and controls in allele distribution of rs1143633 was observed in females (P = 0.0073). A trend towards association was also found between rs16944 and female patients with schizophrenia (P = 0.032).
The present study shows the first evidence that the IL-1β gene polymorphism rs1143633 is associated with schizophrenia susceptibility in a Japanese population. The results suggest the possibility that the influence of IL-1β gene variations on susceptibility to schizophrenia may be greater in females than in males. Findings of the present study provide further support for the role of IL-1β in the etiology of schizophrenia.
有几条证据表明促炎细胞因子白细胞介素-1β（IL-1β）与精神分裂症的病因有关。尽管已经报道了许多遗传关联研究，但很少有研究系统地检查基因广泛的标记多态性。
这项研究共纳入了 533 名精神分裂症患者（302 名男性：平均年龄±标准差 43.4±13.0 岁；233 名女性；平均年龄 44.8±15.3 岁）和 1136 名健康对照者（388 名男性：平均年龄 44.6±17.3 岁；748 名女性；平均年龄 46.3±15.6 岁）。所有研究对象均为生物学上无亲缘关系的日本个体。研究人员检测了白细胞介素-1β基因的 5 个标记多态性（rs2853550、rs1143634、rs1143633、rs1143630、rs16944）与精神分裂症的相关性。
研究人员发现，精神分裂症患者和对照组之间 rs1143633 的等位基因分布存在显著差异（P=0.0089）。在每个性别中分别进行分析时，女性患者和对照组之间 rs1143633 的等位基因分布存在显著差异（P=0.0073）。rs16944 与女性精神分裂症患者之间也存在关联的趋势（P=0.032）。
本研究首次表明，白细胞介素-1β基因多态性 rs1143633 与日本人群的精神分裂症易感性有关。结果表明，白细胞介素-1β基因变异对精神分裂症易感性的影响在女性中可能比男性更大。本研究的结果为白细胞介素-1β在精神分裂症病因学中的作用提供了进一步的支持。
