{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T16:06:16Z","timestamp":1785773176960,"version":"3.56.0"},"reference-count":20,"publisher":"BMJ","issue":"3","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"unspecified","delay-in-days":43,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Spanish Ministry of University","award":["FPU21\/02746"],"award-info":[{"award-number":["FPU21\/02746"]}]},{"name":"Spanish Ministry of Science Innovation and Universities","award":["FPU22\/01652"],"award-info":[{"award-number":["FPU22\/01652"]}]},{"name":"Spanish Ministry of Science Innovation and Universities","award":["PID2022-139292OB-I00"],"award-info":[{"award-number":["PID2022-139292OB-I00"]}]},{"name":"Spanish Ministry of Science Innovation and Universities","award":["PREP2022-000747"],"award-info":[{"award-number":["PREP2022-000747"]}]},{"DOI":"10.13039\/100000090","name":"Congressionally Directed Medical Research Programs","doi-asserted-by":"publisher","award":["DoD-W81XWH-22-1-0162"],"award-info":[{"award-number":["DoD-W81XWH-22-1-0162"]}],"id":[{"id":"10.13039\/100000090","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R01AR081280"],"award-info":[{"award-number":["R01AR081280"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["R33AR078078"],"award-info":[{"award-number":["R33AR078078"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["R61AR078078"],"award-info":[{"award-number":["R61AR078078"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2025,7,26]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The common gain-of-function variant rs35705950, located in the promoter of <jats:italic>MUC5B<\/jats:italic> gene, has been strongly associated with interstitial lung diseases (ILDs) of different aetiology, such as idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-associated ILD (RA-ILD). In this study, we aimed to investigate the association of this variant and its nearby single nucleotide polymorphisms (SNPs) in the largest cohort of systemic sclerosis-associated ILD (SSc-ILD) to date.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Samples were collected from blood\/saliva, followed by DNA extraction and genotyping using SNP arrays. Data for rs35705950 and additional 903 variants within 100\u2009Kb were obtained using genomic imputation. Subsequently, we tested their association in a meta-analysis to increase the consistency of the results, including 10 European ancestry cohorts comprising 2363 patients with SSc-ILD, 3526 SSc patients without ILD and 15\u2009076 controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Meta-analysis showed no significant association between rs35705950 and SSc-ILD, either comparing patients with SSc with and without ILD (p value: 0.588, OR: 1.05, 95% CI: 0.87 to 1.27) nor patients with SSc-ILD with controls (p value: 0.061, OR: 1.16, 95%\u2009CI: 0.99 to 1.36). Moreover, none of the additional 903 variants tested in the genomic region reached statistical significance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Despite analysing the largest and most statistically powered SSc-ILD cohort to date, we found no evidence of association between the <jats:italic>MUC5B<\/jats:italic> promoter variant rs35705950 and its surrounding SNPs with SSc-ILD. These results suggest that the pathogenic mechanisms underlying SSc-ILD may only partially overlap with those of other similar ILDs, such as IPF or RA-ILD. This highlights the need for further studies regarding their genetic architecture.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2025-005754","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T07:30:17Z","timestamp":1755070217000},"page":"e005754","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Assessing the <i>MUC5B<\/i> promoter variant in a large cohort of systemic sclerosis-associated interstitial lung disease"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1257-3338","authenticated-orcid":false,"given":"Carlos","family":"Rosa-Baez","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7697-1696","authenticated-orcid":false,"given":"Carlos","family":"Rangel-Pelaez","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5413-1581","authenticated-orcid":false,"given":"Inmaculada","family":"Rodriguez-Martin","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6298-4514","authenticated-orcid":false,"given":"Martin","family":"Kerick","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Immunology, Institute of Parasitology and Biomedicine Lopez-Neyra, CSIC, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0626-507X","authenticated-orcid":false,"given":"Alfredo","family":"Guillen-Del-Castillo","sequence":"additional","affiliation":[{"name":"Unit of Autoimmune Diseases, Department of Internal Medicine, Hospital Universitario Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen P","family":"Simeon-Aznar","sequence":"additional","affiliation":[{"name":"Unit of Autoimmune Diseases, Department of Internal Medicine, Hospital Universitario Vall d\u2019Hebron, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Callejas","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Hospital San Cecilio, Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre E","family":"Voskuyl","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Amsterdam Rheumatology and immunology Center, Amsterdam UMC, Amsterdam, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Kreuter","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology, and Allergology, Helios St. Elisabeth Klinik Oberhausen, University Witten-Herdecke, Oberhausen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0546-8310","authenticated-orcid":false,"given":"Oliver","family":"Distler","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University Hospital Z\u00fcrich Center of Experimental Rheumatology, Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna M","family":"Proudman","sequence":"additional","affiliation":[{"name":"Rheumatology Unit, Royal Adelaide Hospital and University of Adelaide, Adelaide, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandana","family":"Nikpour","sequence":"additional","affiliation":[{"name":"University of Sydney School of Public Health, Royal Prince Alfred Hospital Sydney, and Sydney MSK Research Flagship Centre, University of Sydney, Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Hunzelmann","sequence":"additional","affiliation":[{"name":"Department of Dermatology and Venereology, University Hospital Cologne, Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5624-1415","authenticated-orcid":false,"given":"Jeska K","family":"De Vries-Bouwstra","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Leiden University Medical Center, Leiden, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4941-7926","authenticated-orcid":false,"given":"Ariane L","family":"Herrick","sequence":"additional","affiliation":[{"name":"Centre for Musculoskeletal Research, The University of Manchester, Northern Care Alliance NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK"},{"name":"NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yannick","family":"Allanore","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Universit\u00e9 Paris Cit\u00e9 UFR de M\u00e9decine, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6529-6258","authenticated-orcid":false,"given":"Lorenzo","family":"Beretta","sequence":"additional","affiliation":[{"name":"Referral Center for Systemic Autoimmune Diseases, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen D","family":"Mayes","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of internal medicine, The University of Texas Health Science Center at Houston, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P","family":"Denton","sequence":"additional","affiliation":[{"name":"Division of Medicine, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shervin","family":"Assassi","sequence":"additional","affiliation":[{"name":"Division of 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