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Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients

BACKGROUND: The genetic architecture of rheumatoid arthritis (RA) and osteoarthritis (OA) are still unclear. Although RA and OA have quite different causes, they share synovial inflammation, risk factors, and some disease-associated genes, including the integrin subunit β2 (ITGB2)/CD18 gene involved...

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Autores principales: Selim, Aliaa M., Elsabagh, Yumn A., El-Sawalhi, Maha M., Ismail, Nabila A., Senousy, Mahmoud A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10463674/
https://www.ncbi.nlm.nih.gov/pubmed/37644537
http://dx.doi.org/10.1186/s12920-023-01635-3
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author Selim, Aliaa M.
Elsabagh, Yumn A.
El-Sawalhi, Maha M.
Ismail, Nabila A.
Senousy, Mahmoud A.
author_facet Selim, Aliaa M.
Elsabagh, Yumn A.
El-Sawalhi, Maha M.
Ismail, Nabila A.
Senousy, Mahmoud A.
author_sort Selim, Aliaa M.
collection PubMed
description BACKGROUND: The genetic architecture of rheumatoid arthritis (RA) and osteoarthritis (OA) are still unclear. Although RA and OA have quite different causes, they share synovial inflammation, risk factors, and some disease-associated genes, including the integrin subunit β2 (ITGB2)/CD18 gene involved in extracellular matrix interactions and immune cell signaling. However, the functional role of ITGB2 genetic variants, its circulating expression pattern, and their clinical usefulness in RA and OA remain unexplored. Our study appraised the association of ITGB2 rs2070946 single nucleotide polymorphism with the vulnerability to RA and OA and its influence on ITGB2 mRNA expression, along with the potential of serum ITGB2 expression in RA and OA diagnosis. METHODS: This study included 70 RA patients, 70 primary OA patients, and 60 healthy volunteers. Genotyping and gene expression analysis were performed using qPCR. Bioinformatics analysis was employed to construct the protein-protein interaction (PPI) network of ITGB2. RESULTS: Serum ITGB2 mRNA expression was upregulated in both RA and OA compared to healthy controls. ITGB2 rs2070946 was associated with escalating risk of both diseases. RA patients harboring the rs2070946 CC or TC + CC genotypes had higher serum ITGB2 expression than the TT genotype carriers. Likewise, OA patients having the minor homozygote CC genotype had higher serum ITGB2 expression than those carrying the TT, TC or TT + TC genotypes. Serum ITGB2 expression showed profound diagnostic potential for RA and OA in receiver-operating characteristic analysis. In RA, serum ITGB2 expression positively correlated with rheumatoid factor and disease activity score 28 (DAS28). The ITGB2-PPI network enriched in cell-cell adhesion, ICAM-3 receptor activity, T-cell activation, leukocyte adhesion, complement binding, and NF-κB, tumor necrosis factor, and interleukin signaling pathways. CONCLUSION: These findings embrace the impact of ITGB2 rs2070946 as a novel genetic biomarker of both RA and OA, which could alter the ITGB2 expression. Serum ITGB2 expression could aid in timely diagnosis of RA and OA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01635-3.
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spelling pubmed-104636742023-08-30 Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients Selim, Aliaa M. Elsabagh, Yumn A. El-Sawalhi, Maha M. Ismail, Nabila A. Senousy, Mahmoud A. BMC Med Genomics Research BACKGROUND: The genetic architecture of rheumatoid arthritis (RA) and osteoarthritis (OA) are still unclear. Although RA and OA have quite different causes, they share synovial inflammation, risk factors, and some disease-associated genes, including the integrin subunit β2 (ITGB2)/CD18 gene involved in extracellular matrix interactions and immune cell signaling. However, the functional role of ITGB2 genetic variants, its circulating expression pattern, and their clinical usefulness in RA and OA remain unexplored. Our study appraised the association of ITGB2 rs2070946 single nucleotide polymorphism with the vulnerability to RA and OA and its influence on ITGB2 mRNA expression, along with the potential of serum ITGB2 expression in RA and OA diagnosis. METHODS: This study included 70 RA patients, 70 primary OA patients, and 60 healthy volunteers. Genotyping and gene expression analysis were performed using qPCR. Bioinformatics analysis was employed to construct the protein-protein interaction (PPI) network of ITGB2. RESULTS: Serum ITGB2 mRNA expression was upregulated in both RA and OA compared to healthy controls. ITGB2 rs2070946 was associated with escalating risk of both diseases. RA patients harboring the rs2070946 CC or TC + CC genotypes had higher serum ITGB2 expression than the TT genotype carriers. Likewise, OA patients having the minor homozygote CC genotype had higher serum ITGB2 expression than those carrying the TT, TC or TT + TC genotypes. Serum ITGB2 expression showed profound diagnostic potential for RA and OA in receiver-operating characteristic analysis. In RA, serum ITGB2 expression positively correlated with rheumatoid factor and disease activity score 28 (DAS28). The ITGB2-PPI network enriched in cell-cell adhesion, ICAM-3 receptor activity, T-cell activation, leukocyte adhesion, complement binding, and NF-κB, tumor necrosis factor, and interleukin signaling pathways. CONCLUSION: These findings embrace the impact of ITGB2 rs2070946 as a novel genetic biomarker of both RA and OA, which could alter the ITGB2 expression. Serum ITGB2 expression could aid in timely diagnosis of RA and OA. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01635-3. BioMed Central 2023-08-29 /pmc/articles/PMC10463674/ /pubmed/37644537 http://dx.doi.org/10.1186/s12920-023-01635-3 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Selim, Aliaa M.
Elsabagh, Yumn A.
El-Sawalhi, Maha M.
Ismail, Nabila A.
Senousy, Mahmoud A.
Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients
title Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients
title_full Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients
title_fullStr Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients
title_full_unstemmed Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients
title_short Association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in Egyptian patients
title_sort association of integrin-β2 polymorphism and expression with the risk of rheumatoid arthritis and osteoarthritis in egyptian patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10463674/
https://www.ncbi.nlm.nih.gov/pubmed/37644537
http://dx.doi.org/10.1186/s12920-023-01635-3
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