Association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritis

Aims: To study factors associated with the development of calcium pyrophosphate (CPP) arthritis and the severity phenotype. Methods: Transversal case-control study. Cases had to be confirmed by both X-ray chondrocalcinosis and CPP crystals in synovial fluid. Controls had neither chondrocalcinosis no...

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Main Authors: Joana Atxotegi-Saenz de Buruaga, Nuria Perez-Herrero, Nerea Perez-Herrero, Cristina Vazquez-Puente, Maria del Consuelo Modesto-Caballero, Fernando Perez-Ruiz
Format: Article
Language:English
Published: Open Exploration Publishing Inc. 2023-10-01
Series:Exploration of Musculoskeletal Diseases
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Online Access:https://www.explorationpub.com/uploads/Article/A100721/100721.pdf
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author Joana Atxotegi-Saenz de Buruaga
Nuria Perez-Herrero
Nerea Perez-Herrero
Cristina Vazquez-Puente
Maria del Consuelo Modesto-Caballero
Fernando Perez-Ruiz
author_facet Joana Atxotegi-Saenz de Buruaga
Nuria Perez-Herrero
Nerea Perez-Herrero
Cristina Vazquez-Puente
Maria del Consuelo Modesto-Caballero
Fernando Perez-Ruiz
author_sort Joana Atxotegi-Saenz de Buruaga
collection DOAJ
description Aims: To study factors associated with the development of calcium pyrophosphate (CPP) arthritis and the severity phenotype. Methods: Transversal case-control study. Cases had to be confirmed by both X-ray chondrocalcinosis and CPP crystals in synovial fluid. Controls had neither chondrocalcinosis nor CPP crystals in synovial fluid. Patients and controls with hemochromatosis or primary hyperparathyroidism were not included. Mutations of hemochromatosis genes (HFE), magnesium (Mg), calcium (Ca), phosphate, iron (Fe), transferrin saturation, ferritin, parathyroid hormone (PTH), and calcifediol levels were studied. Results: Three hundred patients and 300 sex and age matched controls were compared. Lower serum Mg (sMg) and higher ferritin levels were found among patients. Hypomagnesemia (HypoMg) and HFE mutations were more frequent among patients. Involvement of over one joint was observed in 199 (66.4%) patients whereas persistent joint inflammation was retrieved in 154 (51.4%) of the patients. Initial analysis showed that the frequency of polyarticular and inflammatory phenotypes seemed to be progressively overrepresented in patients with HFE mutations. Further bivariate and multivariate analysis adjusted for the time from onset disclosed that the presence of genotypes with C282Y mutations was associated with polyarticular disease (hazard risk 3.501, 95% confidence interval 1.862–6.581, P < 0.001). Although C282Y mutations also seemed to be associated with inflammatory patterns, the association did not reach statistical significance (P = 0.173). Conclusions: Low sMg and high ferritin levels are associated with CPP arthritis (CPPA). In patients without hemochromatosis, HFE mutations, and specifically C282Y mutations seem to associate with the polyarticular disease phenotype, and plausibly with the chronic inflammatory phenotype.
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spelling doaj-art-85b5e29ecdec45b09bb7f0104015770d2025-08-20T02:44:56ZengOpen Exploration Publishing Inc.Exploration of Musculoskeletal Diseases2836-64682023-10-011518619310.37349/emd.2023.00021Association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritisJoana Atxotegi-Saenz de Buruaga0Nuria Perez-Herrero1https://orcid.org/0009-0000-4140-8262Nerea Perez-Herrero2Cristina Vazquez-Puente3Maria del Consuelo Modesto-Caballero4https://orcid.org/0000-0002-4983-5506Fernando Perez-Ruiz5https://orcid.org/0000-0002-5268-1894Osakidetza, OSI EE-Cruces, Rheumatology Division, Cruces University Hospital, 48903 Barakaldo, Spain; BIOBizkaia Health Research Institute, 48903 Barakaldo, SpainDepartment of Medicine, Medicine and Nursery School, University of the Basque Country UPV/EHU, 48903 Barakaldo, SpainUniversity of Deusto, 48007 Bilbao, País Vasco, SpainOsakidetza, OSI EE-Cruces, Rheumatology Division, Cruces University Hospital, 48903 Barakaldo, Spain; BIOBizkaia Health Research Institute, 48903 Barakaldo, SpainOsakidetza, OSI EE-Cruces, Rheumatology Division, Cruces University Hospital, 48903 Barakaldo, Spain; BIOBizkaia Health Research Institute, 48903 Barakaldo, SpainOsakidetza, OSI EE-Cruces, Rheumatology Division, Cruces University Hospital, 48903 Barakaldo, Spain; BIOBizkaia Health Research Institute, 48903 Barakaldo, Spain; Department of Medicine, Medicine and Nursery School, University of the Basque Country UPV/EHU, 48903 Barakaldo, SpainAims: To study factors associated with the development of calcium pyrophosphate (CPP) arthritis and the severity phenotype. Methods: Transversal case-control study. Cases had to be confirmed by both X-ray chondrocalcinosis and CPP crystals in synovial fluid. Controls had neither chondrocalcinosis nor CPP crystals in synovial fluid. Patients and controls with hemochromatosis or primary hyperparathyroidism were not included. Mutations of hemochromatosis genes (HFE), magnesium (Mg), calcium (Ca), phosphate, iron (Fe), transferrin saturation, ferritin, parathyroid hormone (PTH), and calcifediol levels were studied. Results: Three hundred patients and 300 sex and age matched controls were compared. Lower serum Mg (sMg) and higher ferritin levels were found among patients. Hypomagnesemia (HypoMg) and HFE mutations were more frequent among patients. Involvement of over one joint was observed in 199 (66.4%) patients whereas persistent joint inflammation was retrieved in 154 (51.4%) of the patients. Initial analysis showed that the frequency of polyarticular and inflammatory phenotypes seemed to be progressively overrepresented in patients with HFE mutations. Further bivariate and multivariate analysis adjusted for the time from onset disclosed that the presence of genotypes with C282Y mutations was associated with polyarticular disease (hazard risk 3.501, 95% confidence interval 1.862–6.581, P < 0.001). Although C282Y mutations also seemed to be associated with inflammatory patterns, the association did not reach statistical significance (P = 0.173). Conclusions: Low sMg and high ferritin levels are associated with CPP arthritis (CPPA). In patients without hemochromatosis, HFE mutations, and specifically C282Y mutations seem to associate with the polyarticular disease phenotype, and plausibly with the chronic inflammatory phenotype.https://www.explorationpub.com/uploads/Article/A100721/100721.pdfpyrophosphatearthritischondrocalcinosishemochromatosis genes
spellingShingle Joana Atxotegi-Saenz de Buruaga
Nuria Perez-Herrero
Nerea Perez-Herrero
Cristina Vazquez-Puente
Maria del Consuelo Modesto-Caballero
Fernando Perez-Ruiz
Association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritis
Exploration of Musculoskeletal Diseases
pyrophosphate
arthritis
chondrocalcinosis
hemochromatosis genes
title Association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritis
title_full Association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritis
title_fullStr Association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritis
title_full_unstemmed Association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritis
title_short Association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritis
title_sort association of mutations in hemochromatosis genes with clinical severity of calcium pyrophosphate arthritis
topic pyrophosphate
arthritis
chondrocalcinosis
hemochromatosis genes
url https://www.explorationpub.com/uploads/Article/A100721/100721.pdf
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