Diagnostic and Prognostic Risk Assessment of Heat Shock Protein <i>HSPA1B</i> rs2763979 Gene Variant in Asthma

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 <i>HSP70</i> (<i>HSPA1B</i>) gene may impact protein expression and disease phenotype. The <i&...

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Main Authors: Salwa Faisal, Sherouk Abdelaal, Mohammed A. Jeraiby, Fatihi Hassan Soliman Toaimah, Shahad W. Kattan, Abdelhady Ragab Abdel-Gawad, Eman Riad, Eman A. Toraih, Manal S. Fawzy, Ahmed Ibrahim
Format: Article
Language:English
Published: MDPI AG 2022-12-01
Series:Genes
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Online Access:https://www.mdpi.com/2073-4425/13/12/2391
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author Salwa Faisal
Sherouk Abdelaal
Mohammed A. Jeraiby
Fatihi Hassan Soliman Toaimah
Shahad W. Kattan
Abdelhady Ragab Abdel-Gawad
Eman Riad
Eman A. Toraih
Manal S. Fawzy
Ahmed Ibrahim
author_facet Salwa Faisal
Sherouk Abdelaal
Mohammed A. Jeraiby
Fatihi Hassan Soliman Toaimah
Shahad W. Kattan
Abdelhady Ragab Abdel-Gawad
Eman Riad
Eman A. Toraih
Manal S. Fawzy
Ahmed Ibrahim
author_sort Salwa Faisal
collection DOAJ
description 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 <i>HSP70</i> (<i>HSPA1B</i>) gene may impact protein expression and disease phenotype. The <i>HSPA1B</i> 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%, <i>p</i> = 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, <i>p</i> = 0.003), homozygous (OR = 3.35, 95%CI = 1.19–9.39, <i>p</i> = 0.008), dominant (OR = 2.83, 95%CI = 1.52–5.25, <i>p</i> < 0.001), and overdominant (OR = 2.12, 95%CI = 1.20–3.74, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 0.021), and an improvement in peak expiratory flow rate after inhaled salbutamol bronchodilator (<i>p</i> = 0.044) relative to the counterpart genotypes. In conclusion, the <i>HSPA1B</i> 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.
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spelling doaj.art-e66d2112ff6345168766ef3fcb88c8fb2023-11-24T15:06:11ZengMDPI AGGenes2073-44252022-12-011312239110.3390/genes13122391Diagnostic and Prognostic Risk Assessment of Heat Shock Protein <i>HSPA1B</i> rs2763979 Gene Variant in AsthmaSalwa Faisal0Sherouk Abdelaal1Mohammed A. Jeraiby2Fatihi Hassan Soliman Toaimah3Shahad W. Kattan4Abdelhady Ragab Abdel-Gawad5Eman Riad6Eman A. Toraih7Manal S. Fawzy8Ahmed Ibrahim9Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, EgyptDepartment of Pediatrics, Faculty of Medicine, Suez Canal University, Ismailia 41522, EgyptDepartment of Biochemistry, Faculty of Medicine, Jazan University, Jazan 82621, Saudi ArabiaDivision of Pediatric Emergency Medicine, Department of Pediatrics, Hamad Medical Corporation, Doha 3050, QatarDepartment of Medical Laboratory, College of Applied Medical Sciences, Taibah University, Yanbu 46423, Saudi ArabiaDepartment of Clinical and Chemical Pathology, Faculty of Medicine, Sohag University, Sohag 82524, EgyptDepartment of Chest Diseases and Tuberculosis, Faculty of Medicine, Suez Canal University, Ismailia 41522, EgyptDivision of Endocrine and Oncologic Surgery, Department of Surgery, Tulane University School of Medicine, New Orleans, LA 70112, USADepartment of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, EgyptDepartment of Pediatrics, Faculty of Medicine, Suez Canal University, Ismailia 41522, EgyptGiven the significant role the heat shock protein Hsp70 plays in modulating cellular homeostasis in several chronic inflammatory disorders, the genetic variation of the inducible <i>HSP70</i> (<i>HSPA1B</i>) gene may impact protein expression and disease phenotype. The <i>HSPA1B</i> 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%, <i>p</i> = 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, <i>p</i> = 0.003), homozygous (OR = 3.35, 95%CI = 1.19–9.39, <i>p</i> = 0.008), dominant (OR = 2.83, 95%CI = 1.52–5.25, <i>p</i> < 0.001), and overdominant (OR = 2.12, 95%CI = 1.20–3.74, <i>p</i> = 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, <i>p</i> = 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, <i>p</i> = 0.021), and an improvement in peak expiratory flow rate after inhaled salbutamol bronchodilator (<i>p</i> = 0.044) relative to the counterpart genotypes. In conclusion, the <i>HSPA1B</i> 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.https://www.mdpi.com/2073-4425/13/12/2391asthma<i>HSPA1B</i>propensity-matched analysispulmonary function testsreal-time PCRrs2763979
spellingShingle Salwa Faisal
Sherouk Abdelaal
Mohammed A. Jeraiby
Fatihi Hassan Soliman Toaimah
Shahad W. Kattan
Abdelhady Ragab Abdel-Gawad
Eman Riad
Eman A. Toraih
Manal S. Fawzy
Ahmed Ibrahim
Diagnostic and Prognostic Risk Assessment of Heat Shock Protein <i>HSPA1B</i> rs2763979 Gene Variant in Asthma
Genes
asthma
<i>HSPA1B</i>
propensity-matched analysis
pulmonary function tests
real-time PCR
rs2763979
title Diagnostic and Prognostic Risk Assessment of Heat Shock Protein <i>HSPA1B</i> rs2763979 Gene Variant in Asthma
title_full Diagnostic and Prognostic Risk Assessment of Heat Shock Protein <i>HSPA1B</i> rs2763979 Gene Variant in Asthma
title_fullStr Diagnostic and Prognostic Risk Assessment of Heat Shock Protein <i>HSPA1B</i> rs2763979 Gene Variant in Asthma
title_full_unstemmed Diagnostic and Prognostic Risk Assessment of Heat Shock Protein <i>HSPA1B</i> rs2763979 Gene Variant in Asthma
title_short Diagnostic and Prognostic Risk Assessment of Heat Shock Protein <i>HSPA1B</i> rs2763979 Gene Variant in Asthma
title_sort diagnostic and prognostic risk assessment of heat shock protein i hspa1b i rs2763979 gene variant in asthma
topic asthma
<i>HSPA1B</i>
propensity-matched analysis
pulmonary function tests
real-time PCR
rs2763979
url https://www.mdpi.com/2073-4425/13/12/2391
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