Schosser Alexandra, Aschauer Harald N, Wildenauer Dieter B, Schwab Sibylle G, Albus Margot, Maier Wolfgang, Schloegelhofer Monika, Leisch Friedrich, Hornik Kurt, Murray Sarah S, Gasche Christoph
Department of General Psychiatry, University Hospital for Psychiatry, Medical University Vienna, Vienna, Austria.
Am J Med Genet B Neuropsychiatr Genet. 2007 Apr 5;144B(3):347-50. doi: 10.1002/ajmg.b.30416.
Infections of unknown origin and an altered immune response have been hypothesized to play a role in the pathogenesis of schizophrenia. We have previously identified two single nucleotide polymorphisms (SNPs) of the IL-10 receptor 1 (IL-10R1) causing a substitution of glycine 330 to arginine (G330R) and of serine 138 to glycine (S138G). A possible association between these IL-10R1 variants and schizophrenia has been investigated in the present study. DNA of 101 unrelated Austrian patients with a DSM-III-R (Diagnostic and Statistical Manual of Mental Disorders) consensus diagnosis of schizophrenia (n = 70) or schizoaffective disorder (n = 31) and DNA of 121 German schizophrenic patients (DSM-III-R) was analyzed for the presence of S138G and G330R by allele-specific multiplex PCRs. Data from patients were compared with 250 unrelated, psychiatric healthy controls. No difference in allele frequency was detected between patients and controls (G330R: 34.0% vs. 30.0%, P = 0.208; S138G: 19.7% vs. 16.6%, P = 0.235; by Fisher's exact test). However, there was a significant difference in genotype distribution (wt/wt, wt/mut, mut/mut) for G330R between patients (46.8%, 38.3%, 14.9%) and controls (47.6%, 44.8%, 7.6%; Fisher's test P = 0.032). No such difference was seen for S138G. Our results suggest that homozygosity of the IL-10R1 G330R allele is associated with schizophrenia and may contribute to the expression of disease phenotype in susceptible individuals.
不明原因感染和免疫反应改变被认为在精神分裂症的发病机制中起作用。我们之前已鉴定出白细胞介素10受体1（IL-10R1）的两个单核苷酸多态性（SNP），分别导致甘氨酸330被精氨酸替代（G330R）以及丝氨酸138被甘氨酸替代（S138G）。本研究对这些IL-10R1变体与精神分裂症之间可能存在的关联进行了调查。通过等位基因特异性多重PCR分析了101名患有精神分裂症（n = 70）或分裂情感性障碍（n = 31）的奥地利无关患者（依据《精神疾病诊断与统计手册》第三版修订本（DSM-III-R）共识诊断）以及121名德国精神分裂症患者（DSM-III-R）的DNA，以检测S138G和G330R的存在情况。将患者的数据与250名无关的精神健康对照者进行比较。在患者和对照者之间未检测到等位基因频率的差异（G330R：34.0%对30.0%，P = 0.208；S138G：19.7%对16.6%，P = 0.235；采用Fisher精确检验）。然而，患者（46.8%、38.3%、14.9%）和对照者（47.6%、44.8%、7.6%；Fisher检验P = 0.032）之间G330R的基因型分布（野生型/野生型、野生型/突变型、突变型/突变型）存在显著差异。S138G未观察到此类差异。我们的结果表明，IL-10R1 G330R等位基因的纯合性与精神分裂症相关，可能有助于易感个体中疾病表型的表达。
