Association Studies of HSPA1A and HSPA1L Gene Polymorphisms With Schizophrenia.

BACKGROUND:Schizophrenia is a severe psychiatric disorder with a strong genetic component. The HSP70 chaperones are particularly interesting in terms of schizophrenia, especially with regard to neurodevelopmental hypothesis, because they are critical regulators in normal neural physiological function as well as in cell stress responses. AIM OF THE STUDY:The present study aimed to determine whether genetic variants in the (rs1008438, rs562047) and (rs2075800) genes are associated with the risk of paranoid schizophrenia and the clinical presentation of the disease. METHODS:A total of 1080 unrelated Polish subjects of Caucasian origin (401 schizophrenia cases and 679 healthy controls) were recruited. Three single nucleotide polymorphisms (SNP) were genotyped using PCR-RFLP (rs562047) or TaqMan (rs1008438, rs2075800) assays. All analyses were conducted for the full sample and within subgroups stratified by gender. RESULTS:There were no statistically significant differences in genotype or allele distributions of all polymorphisms tested between the schizophrenia and control groups. We also failed to find any schizophrenia predisposing haplotype in the whole group. A sex-stratified analysis revealed haplotypic association with paranoid schizophrenia in men, albeit the risk effect was contributed only by a rare haplotypes. More importantly, rs562047 variant was significantly associated with PANSS total and PANSS negative scores in schizophrenia. CONCLUSIONS:Our results support previously reported associations between Hduanyu18421A and SNPs and schizophrenia symptomatology. Further population-based prospective studies with larger sample sizes from different ethnic groups should be performed to clarify the role of different HSP70 genes in the pathogenesis of schizophrenia.

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