Department of Medical Genetics, Medical University of Silesia, Ostrogorska 30, 41-200, Sosnowiec, Poland,
Cell Stress Chaperones. 2014 Mar;19(2):205-15. doi: 10.1007/s12192-013-0446-7. Epub 2013 Jul 28.
HSP70 genes have been considered as promising schizophrenia candidate genes based on their protective role in the central nervous system under stress conditions. In this study, we analyzed the potential implication of HSPA1A +190G/C, HSPA1B +1267A/G, and HSPA1L +2437T/C polymorphisms in the susceptibility to paranoid schizophrenia in a homogenous Caucasian Polish population. In addition, we investigated the association of the polymorphisms with the clinical variables of the disease. Two hundred and three patients with paranoid schizophrenia and 243 healthy controls were enrolled in the study. Polymorphisms of HSPA1A, -1B, and -1L genes were genotyped using the PCR-RFLP technique. Analyses were conducted in entire groups and in subgroups that were stratified according to gender. There were significant differences in the genotype and allele frequencies of HSPA1A polymorphism between the patients and controls. The +190CC genotype and +190C allele were over-represented in the patients and significantly increased the risk for developing schizophrenia (OR = 3.45 and OR = 1.61, respectively). Interestingly, such a risk was higher for females with the +190CC genotype than for males with the +190CC genotype (OR = 5.78 vs. OR = 2.76). We also identified the CGT haplotype as a risk haplotype for schizophrenia and demonstrated the effects of HSPA1A and HSPA1B genotypes on the psychopathology and age of onset. Our study provided the first evidence that the HSPA1A polymorphism may potentially increase the risk of developing paranoid schizophrenia. Further independent analyses in different populations to evaluate the role of gender are needed to replicate these results.
热休克蛋白 70 基因(HSP70 genes)因其在应激条件下对中枢神经系统的保护作用,被认为是精神分裂症的候选基因。本研究旨在分析 HSPAA1A+190G/C、HSPA1B+1267A/G 和 HSPA1L+2437T/C 多态性在同质的波兰白种人群中对偏执型精神分裂症易感性的潜在影响。此外,我们还研究了这些多态性与疾病临床变量的相关性。共纳入 203 例偏执型精神分裂症患者和 243 例健康对照者。采用 PCR-RFLP 技术对 HSPAA1、-1B 和-1L 基因的多态性进行基因分型。在整个研究组和根据性别分层的亚组中进行了分析。在患者和对照组之间,HSPA1A 多态性的基因型和等位基因频率存在显著差异。+190CC 基因型和+190C 等位基因在患者中更为常见,显著增加了患精神分裂症的风险(OR=3.45 和 OR=1.61)。有趣的是,女性携带+190CC 基因型的风险高于男性携带+190CC 基因型的风险(OR=5.78 比 OR=2.76)。我们还发现 CGT 单倍型是精神分裂症的风险单倍型,并证明了 HSPA1A 和 HSPA1B 基因型对精神病理学和发病年龄的影响。本研究首次提供了证据表明,HSPA1A 多态性可能会增加偏执型精神分裂症的发病风险。需要在不同人群中进行独立分析以评估性别作用,从而复制这些结果。