PDF(Pubmed)
Abstract：
Heat shock cognate 70 (HSC70/HSPA8) is considered to be a promising candidate gene for schizophrenia (SCZ) due to its many essential functions and potential neuroprotective properties in the CNS (e.g., HSC70 is involved in the turnover of the synaptic proteins, synaptic vesicle recycling, and neurotransmitter homeostasis). An alteration in the expression of HSPA8 in SCZ has been reported. This implies that the genetic variants of HSPA8 might contribute to schizophrenia pathogenesis. The present study attempted to determine whether HSPA8 polymorphisms are associated with a susceptibility to schizophrenia or whether they have an impact on the clinical parameters of the disease in a Polish population. A total of 1066 participants (406 patients and 660 controls) were recruited for the study. Five SNPs of the HSPA8 gene (rs2236659, rs1136141, rs10892958, rs1461496, and rs4936770) were genotyped using TaqMan assays. There were no differences in the allele or genotype distribution in any of the SNPs in the entire sample. We also did not find any HSPA8 haplotype-specific associations with SCZ. A gender stratification analysis revealed that an increasing risk of schizophrenia was associated with the rs1461496 genotype in females (OR: 1.68, p < 0.05) in the recessive model. In addition, we found novel associations between HSPA8 SNPs (rs1136141, rs1461496, and rs10892958) and the severity of the psychiatric symptoms as measured by the PANSS. Further studies with larger samples from various ethnic groups are necessary to confirm our findings. Furthermore, studies that explore the functional contribution of the HSPA8 variants to schizophrenia pathogenesis are also needed.
摘要：
热休克同源70（HSC70/HSPA8）被认为是精神分裂症（SCZ）的有希望的候选基因，因为它在中枢神经系统中具有许多基本功能和潜在的神经保护特性（例如，HSC70参与突触蛋白的周转，突触小泡再循环，和神经递质稳态)。已经报道了SCZ中HSPA8表达的改变。这表明HSPA8的遗传变异可能与精神分裂症的发病机理有关。本研究试图确定HSPA8多态性是否与精神分裂症易感性相关，或者它们是否对波兰人群的疾病临床参数有影响。总共招募了1066名参与者（406名患者和660名对照）进行研究。使用TaqMan测定法对HSPA8基因的五个SNP(rs2236659、rs1136141、rs10892958、rs1461496和rs4936770)进行基因分型。整个样品中任何SNP的等位基因或基因型分布均无差异。我们也没有发现任何与SCZ的HSPA8单倍型特异性关联。性别分层分析显示，在隐性模型中，女性精神分裂症的风险增加与rs1461496基因型相关（OR：1.68，p<0.05）。此外,我们发现HSPA8SNP(rs1136141,rs1461496和rs10892958)与PANSS测量的精神症状严重程度之间存在新的关联.有必要对来自各个种族的更大样本进行进一步研究，以证实我们的发现。此外，还需要探索HSPA8变异体对精神分裂症发病机制的功能贡献的研究。
