Malgorzata Kowalczyk1, Krzysztof Kucia2, Aleksander Owczarek3, Renata Suchanek-Raif4, Wojciech Merk2, Monika Paul-Samojedny4, Jan Kowalski4. 1. Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jednosci 8, 41-200 Sosnowiec, Poland. Electronic address: malgorzata.kowalczyk@sum.edu.pl. 2. Department of Psychiatry and Psychotherapy, School of Medicine, Medical University of Silesia, Katowice, Ziolowa 45, 40-635, Katowice, Poland. 3. Division of Statistics, Department of Instrumental Analysis, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Ostrogorska 30, 41-200 Sosnowiec, Poland. 4. Department of Medical Genetics, School of Pharmacy with the Division of Laboratory Medicine, Medical University of Silesia, Jednosci 8, 41-200 Sosnowiec, Poland.
Abstract
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 HSPA1A (rs1008438, rs562047) and HSPA1L (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 HSPA1A and HSPA1B 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.
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 HSPA1A (rs1008438, rs562047) and HSPA1L (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 HSPA1A and HSPA1B 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.