T93. ASSOCIATION ANALYSIS POLYMORPHISMS OF THE HEAT SHOCK PROTEINS (HSPS) WITH SCHIZOPHRENIA

• Published in: European neuropsychopharmacology Vol. 75; p. S212
• Main Authors: Sepe, Lucas, Xu, Junzhe, Li, Daniel
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2023
• DOI: 10.1016/j.euroneuro.2023.08.377
• ISSN: 0924-977X

Schizophrenia is a severe psychiatric disorder with a strong genetic component. The heat shock protein 70 (HSP70) is believed to be involved in the pathogenesis of schizophrenia with regard to neurodevelopment. An aberration in the HSP70 has been proposed in schizophrenia patients, suggesting that it is a candidate gene for schizophrenia. Heat shock proteins (HSPs) are a promising candidate gene in schizophrenia as they are believed to play a protective role in the central nervous system. An alteration in the titers of antibodies to the HSPs in schizophrenia patients has been suggested. Association between the three polymorphisms of HSP70-1 (HSPA1A), HSP70-hom (HSPA1L), and HSP70-2 (HSPA1B) and schizophrenia has been reported. Therefore, this study investigated the association between two single nucleotide polymorphisms at the HSP70 gene and schizophrenia. In this study, we analyzed the potential implication of HSPA1A +190G/C and HSPA1L +2437T/C polymorphisms in the susceptibility to paranoid schizophrenia. After informed consent was obtained, 100 schizophrenia patients and 100 control subjects were enrolled in this study. All subjects were administered the Diagnostic Interview for Genetic Studies (DIGS) (National Institute of Mental Health-Molecular Genetics Initiative, 1992; Nurnberger et al., 1994) by research assistants with extensive training in this interview. Blood samples were collected in anonymously identified 10-ml Vacutainer tubes. DNA was prepared by a modified SDS/Proteinase K procedure. Two single nucleotide polymorphisms (SNP) HSPA1A +190G/C and HSPA1L +2437T/C polymorphisms were genotyped using PCR-RFLP. We analyzed polymorphisms +190G/C in the HSPA1A (rs1043618) and +2437T/C in the HSPA1L (rs2227956) of HSP70 genes. There are no statistically significant differences in genotype or allele distributions of +190G/C in the HSPA1A (rs1043618) gene. More importantly, there is a significant association between the HSPA1L (rs2227956) polymorphism of HSP70 genes with schizophrenia (Fisher is 0.0004). The HSP70 chaperones are particularly interesting in terms of schizophrenia, especially with regard to the neurodevelopmental hypothesis, because they are critical regulators in normal neural physiological function as well as in cell stress responses. HSP70 is an interesting molecular chaperone with regard to neurodevelopmental abnormalities and immune dysregulation to the etiopathogenesis of schizophrenia. The HSP70 is essential for the repair or removal of defective proteins as a result of various mechanical or chemical stresses, including oxidative free radicals and toxic metals, and plays a major role during normal growth and differentiation of mammalian cells. This study focused on two genes, HSP70-1 (HSPA1A) and HSP70-hom (HSPA1L) because they are located at 6p21.3 in the HLA class III region, which has been implicated in the susceptibility to schizophrenia, as evidenced by some linkage and association studies.