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.