Association of HSPA1B Polymorphisms with Paranoid Schizophrenia in a Polish Population

Kowalczyk, Małgorzata; Kucia, Krzysztof; Owczarek, Aleksander; Suchanek-Raif, Renata; Merk, Wojciech; Fila-Daniłow, Anna; Paul-Samojedny, Monika; Choręża, Piotr; Kowalski, Jan

doi:10.1007/s12017-019-08575-1

Cited by 11 publications

(11 citation statements)

References 46 publications

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“…The current study failed to demonstrate any associations between the HSPB1 variants and suicidal behavior in either the entire sample or in the gender-stratified analysis. However, we did find a strong significant association between the HSPA1B rs539689 polymorphism and attempted suicide in patients with SCZ in our previous study [ 30 ]. The C/C genotype and C allele were protective against suicidal behavior in all of the samples as well as in the male and female subgroups.…”

Section: Discussionmentioning

confidence: 66%

“…Initial analyses with positive findings were performed on a Korean population [ 25 , 26 ]. More recently, the case-control studies performed by our group in a Polish population provided evidence that the HSPA1A (rs1043618) and HSPA1B (rs539689) polymorphisms might be involved in the susceptibility to SCZ in a sex-dependent manner [ 28 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…In the same study, significant differences were also observed in the age of onset between males and females among the HSPA1A rs1043618 genotypes [ 28 ]. We also detected the influence of the HSPA1B rs539689 genotype on the positive, general, and total PANSS scores and the association between the HSPA1B rs9281590 genotype, gender, and the general PANSS scores [ 30 ]. Finally, HSPA1A rs562047 was significantly associated with the PANSS total and PANSS negative scores [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

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HSPB1 Gene Variants and Schizophrenia: A Case-Control Study in a Polish Population

et al. 2022

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Schizophrenia (SCZ) is a severe psychiatric disorder that has a significant genetic component. HSPB1 (HSP27) is known for its neuroprotective functions under stress conditions and appears to play an important role during the development of the central nervous system, which is in agreement with the neurodevelopmental hypothesis of SCZ. The aim of the present case-control study was to investigate whether HSPB1 variants contribute to the risk and clinical features (age of onset, symptoms, and suicidal behavior) of SCZ in a Polish population. To the best of our knowledge, this is the first study that investigated the association between the HSPB1 polymorphisms and SCZ. Three SNPs of HSPB1 (rs2868370, rs2868371, and rs7459185) were genotyped in a total of 1082 (403 patients and 679 controls) unrelated subjects using TaqMan assays. The results showed that the genotypes, alleles, and haplotypes of the three SNPs were not significantly different between the schizophrenic patients and healthy controls either in the overall analysis or in the gender-stratified analysis (all p > 0.05 ). However, we did find a significant effect of the rs2868371 genotype on the age of onset, negative symptoms, and disorganized symptoms in the five-factor model of PANSS (all p < 0.01 ). Post hoc comparisons showed that carriers of the rs2868371 G/G genotype had significantly higher negative and disorganized factor scores than those with the C/G and C/C genotypes, respectively. Further investigations with other larger independent samples are required to confirm our findings and to better explore the effect of the HSPB1 polymorphisms on the risk and symptomatology of SCZ.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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HSPB1 Gene Variants and Schizophrenia: A Case-Control Study in a Polish Population

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“…It is worth noting that the HSPA8 polymorphisms primarily influenced the positive SCZ symptoms (delusions, hallucinations, disorganized speech) in this work. Our previous studies reported a correlation between the HSPA1A (rs1043618) and HSPA1B (rs539689 and rs1061581) polymorphisms and positive symptoms in SCZ patients (Kowalczyk et al 2014(Kowalczyk et al , 2020. Pae et al (2009) also found an association between the HSPA1B rs539689 SNP and PANSS-positive scores at discharge in their experiment investigating the impact of the HSP70 polymorphisms on the clinical symptoms and drug response in schizophrenic patients.…”

Section: Discussionmentioning

confidence: 91%

“…Previous studies have identified an altered expression of HSPA8 in SCZ patients (Föcking et al 2015;Guan et al 2019). Genetic variations of other HSP70 genes (HSPA1A, -1B, -1L) have also been associated with an increased risk of SCZ and the clinical variables of the disease (Pae et al 2005(Pae et al , 2009Kim et al 2008;Kowalczyk et al 2014Kowalczyk et al , 2018Kowalczyk et al , 2020. One study revealed a difference in the HSPA8 rs1136141 polymorphism between first-episode psychotic schizophrenic patients and healthy participants (Bozidis et al 2014).…”

Section: Introductionmentioning

confidence: 99%

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

Kowalczyk

Owczarek

Suchanek-Raif

et al. 2022

Cell Stress and Chaperones

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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.

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Genetics of suicide ideation. A role for inflammation and neuroplasticity?

Turiaco,

Iannuzzo,

Bruno

et al. 2024

Eur Arch Psychiatry Clin Neurosci

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Suicide is a leading cause of death worldwide. Suicide ideation (SI) is a known risk factor for suicide behaviour (SB). The current psychobiology and genetic predisposition to SI and SB are poorly defined. Despite convincing relevance of a genetic background for SI, there is no current implementable knowledge about the genetic makeup that identifies subjects at risk for it. One of the possible reasons for the absence of a clear-cut evidence is the polygenetic nature of SI along with the very large sample sizes that are needed to observe significant genetic association result. The CATIE sample was instrumental to the analysis. SI was retrieved as measured by the Calgary test. Clinical possible covariates were identified by a nested regression model. A principal component analysis helped in defining the possible genetic stratification factors. A GWAS analysis, polygenic risk score associated with a random forest analysis and a molecular pathway analysis were undertaken to identify the genetic contribution to SI. As a result, 741 Schizophrenic individuals from the CATIE were available for the genetic analysis, including 166,325 SNPs after quality control and pruning. No GWAS significant result was found. The random forest analysis conducted by combining the polygenic risk score and several clinical variables resulted in a possibly overfitting model (OOB error rate < 1%). The molecular pathway analysis revealed several molecular pathways possibly involved in SI, of which those involved in microglia functioning were of particular interest. A medium-small sample of SKZ individuals was analyzed to shed a light on the genetic of SI. As an expected result from the underpowered sample, no GWAS positive result was retrieved, but the molecular pathway analysis indicated a possible role of microglia and neurodevelopment in SI.

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Association of HSPA1B Polymorphisms with Paranoid Schizophrenia in a Polish Population

Cited by 11 publications

References 46 publications

HSPB1 Gene Variants and Schizophrenia: A Case-Control Study in a Polish Population

HSPB1 Gene Variants and Schizophrenia: A Case-Control Study in a Polish Population

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

Genetics of suicide ideation. A role for inflammation and neuroplasticity?

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