An association study of the HSPA8 gene polymorphisms with schizophrenia in a Polish population

Cell Stress Chaperones. 2022 Jan;27(1):71-82. doi: 10.1007/s12192-021-01249-7. Epub 2021 Dec 21.

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.

Keywords: Case–control study; HSPA8/HSC70; PANSS; Schizophrenia; Single-nucleotide polymorphism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HSC70 Heat-Shock Proteins / genetics
  • Humans
  • Poland / epidemiology
  • Polymorphism, Single Nucleotide / genetics
  • Schizophrenia* / epidemiology
  • Schizophrenia* / genetics

Substances

  • HSC70 Heat-Shock Proteins
  • HSPA8 protein, human