Diagnostic and Prognostic Risk Assessment of Heat Shock Protein HSPA1B rs2763979 Gene Variant in Asthma

Abstract

Given the significant role the heat shock protein Hsp70 plays in modulating cellular homeostasis in several chronic inflammatory disorders, the genetic variation of the inducible HSP70 (HSPA1B) gene may impact protein expression and disease phenotype. The HSPA1B rs2763979 variant has been associated with multiple inflammatory scenarios, but no previous studies have explored its association with asthma. In this sense, this cross-sectional study enrolled 90 children with asthma and 218 age-/sex-matched healthy volunteers for rs2763979 variant genotyping by TaqMan allelic discrimination analysis. The results were investigated under several genetic models and associated with disease susceptibility and clinicolaboratory data. Overall analysis, including the 308 participants, revealed a higher C allele frequency among patients relative to controls (43.0% vs. 33%, p = 0.006). Furthermore, patients with the C variant initially had a higher risk of asthma under heterozygous (OR = 2.75, 95%CI = 1.46–5.18, p = 0.003), homozygous (OR = 3.35, 95%CI = 1.19–9.39, p = 0.008), dominant (OR = 2.83, 95%CI = 1.52–5.25, p < 0.001), and overdominant (OR = 2.12, 95%CI = 1.20–3.74, p = 0.008) models. However, after employing a 1:1 nearest propensity matching analysis, the studied variant showed only borderline significance with asthma under the dominant model in 71 matched cohorts. Interestingly, patients who carry the rs2763979 CC genotype showed favorable spirometric parameters in terms of better (mean ± SD) forced vital capacity (86.3 ± 7.4 vs. 77.7 ± 6.1 and 75.7 ± 7.2 for CT and TT, respectively, p = 0.021), forced expiratory volume in one second before bronchodilation (60.7 ± 12.9 vs. 54.9 ± 7.6 and 56.1 ± 7.5 for CT and TT, respectively, p = 0.021), and an improvement in peak expiratory flow rate after inhaled salbutamol bronchodilator (p = 0.044) relative to the counterpart genotypes. In conclusion, the HSPA1B rs2763979 variant might have prognostic utility as a genetic marker for asthma in our population. Further larger studies on different ethnicities are recommended to validate the results.

Deciphering the Immune Subtypes and Signature Genes: A Novel Approach Towards Diagnosing and Prognosticating Severe Asthma through Interpretable Machine Learning

“…CTLA4, which encodes the cytotoxic T-lymphocyte antigen-4, influences the immune response; its gene variants show diverse links to asthma risk, severity, and treatment outcomes 44 . HSPA1A, a member of the heat shock protein 70 family, contributes to asthma by enhancing airway inflammation via increased production of pro-inflammatory cytokines and chemokines 45,46 . CD4, which encodes a receptor on helper T cells, plays a role in asthma through airway inflammation and sensitivity, with CD4+ T cells releasing pro-inflammatory cytokines when exposed to allergens 47,48 .…”

The transcriptomic signature of respiratory sensitizers using an alveolar model

“…Among DCs, the known sensitizer IPDI upregulated genes associated with cellular responses to stress, metabolism, membrane trafficking, transcription, and mRNA splicing (Sucre et al 2018 ; Marciano et al 2021 ; Domanegg et al 2022 ; Faisal et al 2022 ; Liang et al 2022 ), while genes associated with preventing allergy, such as type I hypersensitivity and airway hyperresponsiveness, (Dharajiya et al 2010 ; Übel et al 2014 ) were consistently downregulated. Interestingly, regardless of which non-sensitizer was used, there were two upregulated genes among AMs and epithelial cells associated with airway hyperresponsiveness and allergy ( CCL3L1 , GJD3 ), and among DCs, there were 5 upregulated genes in common also associated with airway allergy and inflammation ( SOX9 , UACA , CCDC88A , FOSL1 , KIF20B ) (Laulajainen-Hongisto et al 2020 ; Jiang et al 2021 ; Bao and Zhu 2022 ).…”

Single-cell RNA sequencing reveals cell subpopulations in the tumor microenvironment contributing to hepatocellular carcinoma

“…The HSPA1B + Tcm subpopulation was significantly increased in the HCC group, and HSPA1B was significantly enriched in all cell types in the HCC group, suggesting its involvement in remodeling of the tumor ecological niche in HCC. HSPA1B belongs to heat shock protein family A, where the binding of other heat shock proteins can stabilize existing proteins and mediate the folding of newly translated proteins in the cytosol and organelles (Faisal et al, 2022). Moreover, HSPA1B is involved in the ubiquitin-proteasome pathway through interaction with the AU-rich element RNA-binding protein 1, and the ubiquitin-proteasome system is an important non-lysosomal protein degradation pathway in cells that directly or indirectly affects the occurrence of various malignant tumors by regulating cell cycle activity and apoptosis-related proteins and activating or inhibiting the expression of proto-oncogenes and anti-oncogenes (Park et al, 2020).…”