Academic Journal
Phenotype-specific associations of mosaic chromosomal alterations in systemic sclerosis.
| Τίτλος: | Phenotype-specific associations of mosaic chromosomal alterations in systemic sclerosis. |
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| Συγγραφείς: | Nishio Y; RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics, Yokohama, Japan; Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan; Department of Statistical and Translational Genetics, Center for Genomic Medicine, Fujita Health University 1-98 Dengakugakubo, Kutsukake-cho,Toyoake, Aichi 470-1192, Japan; Shizuoka General Hospital, The Clinical Research Center, Shizuoka, Japan., Ishikawa Y; RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics, Yokohama, Japan; Department of Statistical and Translational Genetics, Center for Genomic Medicine, Fujita Health University 1-98 Dengakugakubo, Kutsukake-cho,Toyoake, Aichi 470-1192, Japan; Shizuoka General Hospital, The Clinical Research Center, Shizuoka, Japan., Uchiyama S; Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan., Liu X; RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics, Yokohama, Japan., Takada S; RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics, Yokohama, Japan., Kuroshima T; RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics, Yokohama, Japan., Yoshifuji H; Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Kodera M; Department of Dermatology, Chukyo Hospital, Japan Community Health Care Organization, Nagoya, Japan., Akahoshi M; Department of Rheumatology, Faculty of Medicine, Saga University, Saga, Japan., Niiro H; Department of Medical Education, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan., Motegi SI; Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan., Shirai Y; Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan., Nakayama Y; Laboratory of Immunopathogenesis, Institute for Life and Medical Sciences, Kyoto University, Kyoto, Japan., Hirobe K; Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Nakashima R; Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Endo Y; Department of Dermatology, Gunma University Graduate School of Medicine, Maebashi, Japan., Hasegawa M; Faculty of Medical Sciences, Department of Dermatology, University of Fukui, Fukui, Japan., Asano Y; Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan; Department of Dermatology, The University of Tokyo, Tokyo, Japan., Nakayamada S; The First Department of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan., Tanaka Y; Department of Molecular Targeted Therapeutics, University of Occupational and Environmental Health, Kitakyushu, Japan., Koyanagi YN; Division of Cancer Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan., Matsuo K; Department of Cancer Epidemiology, Nagoya University Graduate School of Medicine, Nagoya, Japan; Tokyo Women's Medical University, Division of Rheumatology, Department of Internal Medicine, Tokyo, Japan., Kawaguchi Y; Tokyo Women's Medical University, Division of Rheumatology, Department of Internal Medicine, Tokyo, Japan., Kuwana M; Department of Allergy and Rheumatology, Nippon Medical School Graduate School of Medicine, Tokyo, Japan., Imoto I; Aichi Cancer Center Research Institute, Nagoya, Japan., Yamaguchi Y; Department of Environmental Immuno-Dermatology, Yokohama City University Graduate School of Medicine, Yokohama, Japan., Terao C; RIKEN Center for Integrative Medical Sciences, The Laboratory for Statistical and Translational Genetics, Yokohama, Japan; Department of Statistical and Translational Genetics, Center for Genomic Medicine, Fujita Health University 1-98 Dengakugakubo, Kutsukake-cho,Toyoake, Aichi 470-1192, Japan; Shizuoka General Hospital, The Clinical Research Center, Shizuoka, Japan; The Department of Applied Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. Electronic address: chikashi@fujita-hu.ac.jp. |
| Πηγή: | Annals of the rheumatic diseases [Ann Rheum Dis] 2026 Oct; Vol. 85 (10), pp. 2022-2032. Date of Electronic Publication: 2026 Jul 09. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: BMJ Country of Publication: United States NLM ID: 0372355 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-2060 (Electronic) Linking ISSN: 00034967 NLM ISO Abbreviation: Ann Rheum Dis Subsets: MEDLINE |
| Imprint Name(s): | Publication: London : BMJ Original Publication: London : H.K. Lewis |
| Ιατρικοί όροι (MeSH): | Scleroderma, Systemic*/genetics , Scleroderma, Systemic*/immunology , Scleroderma, Systemic*/complications , Mosaicism* , Chromosome Aberrations*, Autoantibodies/blood ; Chromosomes, Human, X/genetics ; Humans ; Female ; Phenotype ; Middle Aged ; Male ; Adult ; Aged ; Age of Onset ; Case-Control Studies |
| Περίληψη: | Objectives: Mosaic chromosomal alterations (mCAs) increase with age and are associated with many diseases, including autoimmune diseases. The associations between mCAs and systemic sclerosis (SSc) and its clinical subtypes have not been explored. Methods: We recruited study subjects from 2 independent datasets (set 1: 635 SSc, 4401 controls; set 2: 347 SSc, 2170 controls) and detected mCAs (loss, loss of heterozygosity [LOH], gain, and mosaic loss of the X chromosome [mLOX]) from their peripheral blood samples. Logistic regression analyses were conducted with covariates in each cohort, and the results were meta-analysed. We also conducted stratified analyses by age groups, the age at disease onset, clinical phenotypes based on the skin lesions, autoantibody profiles, and the presence of complications. Results: We observed a trend of increased loss in SSc, especially in old age (P = .0063). The association of loss was strengthened in certain subtypes of SSc, including lcSSc (odds ratio [OR] = 2.22, P = .019) and SSc with vascular complications (digital ulcers, pulmonary hypertension, or renal crisis; OR = 3.30, P = .0054). The effect sizes of Loss increased in patients with high cell fractions (CFs). We also observed that mLOX was significantly associated with SSc, limited cutaneous systemic sclerosis (lcSSc), and anticentromere antibody-positive systemic sclerosis (ACA-SSc) only for subjects with high CFs. mLOX was significantly associated with lcSSc and ACA-SSc even compared with dcSSc and ATA-SSc, respectively. These associations were consistently observed in each of the 2 datasets. Finally, we identified majority of the associations of Loss were mainly driven by SSc with late age at onset. Conclusions: Loss and mLOX were significantly and differentially associated with SSc and its subtypes, underscoring potential phenotype-specific contributions of mCAs. (Copyright © 2026 European Alliance of Associations for Rheumatology (EULAR). Published by Elsevier B.V. All rights reserved.) |
| Substance Nomenclature: | 0 (Autoantibodies) |
| Entry Date(s): | Date Created: 20260709 Date Completed: 20261003 Latest Revision: 20261003 |
| Update Code: | 20261004 |
| DOI: | 10.1016/j.ard.2026.06.006 |
| PMID: | 42425799 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1468-2060 |
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| DOI: | 10.1016/j.ard.2026.06.006 |