Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jednosci 8, 41-200, Sosnowiec, Poland.
Department of Psychiatry and Psychotherapy, School of Medicine, Medical University of Silesia, Katowice, Ziolowa 45, 40-635, Katowice, Poland.
Neuromolecular Med. 2020 Mar;22(1):159-169. doi: 10.1007/s12017-019-08575-1. Epub 2019 Oct 23.
This study aimed to find the potential association between HSPA1B polymorphisms and risk of paranoid schizophrenia, clinical variables of the disease, and suicidal behavior. A total of 901 unrelated Polish subjects of Caucasian origin (377 schizophrenia patients and 524 controls) were recruited. Four single-nucleotide polymorphisms (SNP) were genotyped using PCR-RFLP (rs539689, rs9281590) and TaqMan assays (rs263979, rs6547452). A strong tendency towards statistical significance (p = 0.051) was observed in rs539689 allele distribution between patients and controls in overall study subjects. After stratification according to gender, we found that rs539689 was significantly associated with schizophrenia in males, but not in females. The minor allele C had a protective effect in males [OR 0.73 (95% CI 0.61-0.88, p < 0.05)]. In addition, two SNPs (rs539689, rs9281590) were significantly associated with PANSS scores. Another important finding was a strong significant association between the HSPA1B rs539689 polymorphism and attempted suicide in schizophrenic patients. The C/C genotype and C allele were protective against suicidal behavior in entire sample (p < 0.001), in males (p < 001), and in females (p < 0.05), although associations were weaker than in males. Our findings support that HSPA1B gene may be involved in susceptibility to schizophrenia and clinical presentation of the disease in a sex-dependent manner, and may play a role in suicidal behavior in the Polish population of schizophrenic patients. Further independent analyses in different populations should be performed to clarify the role of HSPA1B in the pathogenesis of schizophrenia.
本研究旨在探讨 HSPA1B 多态性与偏执型精神分裂症风险、疾病临床变量和自杀行为之间的潜在关联。共纳入 901 名无血缘关系的白种人波兰受试者(377 名精神分裂症患者和 524 名对照)。采用 PCR-RFLP(rs539689、rs9281590)和 TaqMan 分析方法对 4 个单核苷酸多态性(SNP)进行基因分型(rs263979、rs6547452)。在所有研究对象中,患者和对照组之间 rs539689 等位基因分布存在显著的统计学趋势(p=0.051)。根据性别分层后,我们发现 rs539689 与男性精神分裂症显著相关,但与女性无关。次要等位基因 C 具有保护作用[OR 0.73(95% CI 0.61-0.88,p<0.05)]。此外,两个 SNP(rs539689、rs9281590)与 PANSS 评分显著相关。另一个重要发现是 HSPA1B rs539689 多态性与精神分裂症患者自杀企图之间存在强烈的显著关联。C/C 基因型和 C 等位基因对整个样本(p<0.001)、男性(p<001)和女性(p<0.05)的自杀行为具有保护作用,尽管关联在男性中较弱。我们的研究结果支持 HSPA1B 基因可能以性别依赖的方式参与精神分裂症的易感性和疾病的临床表现,并可能在波兰精神分裂症患者的自杀行为中发挥作用。应在不同人群中进行进一步的独立分析,以阐明 HSPA1B 在精神分裂症发病机制中的作用。