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dc.contributor.authorJones, Garan
dc.contributor.authorPilling, L. C.
dc.contributor.authorMelzer, David
dc.date.accessioned2021-06-08T13:02:57Z
dc.date.available2021-06-08T13:02:57Z
dc.date.issued2020-01-20
dc.identifier.citationJones G et al. Sarcopenia and Variation in the Human Leukocyte Antigen Complex. J Gerontol A Biol Sci Med Sci. 2020 Jan 20;75(2):301-308.en_US
dc.identifier.pmid30772894
dc.identifier.doi10.1093/gerona/glz042
dc.identifier.urihttps://rde.dspace-express.com/handle/11287/621752
dc.description.abstractBackground: Aging is characterized by chronic inflammation plus loss of muscle mass and strength, termed sarcopenia. Human leukocyte antigen (HLA) types are drivers of autoimmune disease, although with limited penetrance. We tested whether autoimmune diagnoses are associated with sarcopenia, and whether HLA types and related genetic variants are associated with sarcopenia in autoimmune disease-free older people. Methods: Data were collected from 181,301 UK Biobank European descent volunteers aged 60-70 with measured hand grip strength and impedance. Logistic regression analysis estimated HLA type and sarcopenia associations, adjusted for confounders and multiple testing. Results: Having any autoimmune diagnosis was associated with sarcopenia (odds ratio [OR] 1.83, 95% confidence interval (CI) 1.74-1.92, p = 4.0*10-125). After excluding autoimmune diagnoses, 6 of 100 HLA types (allele frequency >1%) were associated with sarcopenia (low grip strength and muscle mass). Having two HLA-DQA1*03:01 alleles increased odds of sarcopenia by 19.3% (OR 1.19, CI 1.09-1.29, p = 2.84*10-5), compared to no alleles. Having ≥6 of the 12 HLA alleles increased sarcopenia odds by 23% (OR 1.23, CI 1.12-1.35, p = 7.28*10-6). Of 658 HLA region non-coding genetic variants previously implicated in disease, 4 were associated with sarcopenia, including rs41268896 and rs29268645 (OR 1.08, CI 1.05-1.11, p = 1.06*10-8 and 1.07, CI 1.04-1.09, p = 1.5*10-6, respectively). Some HLA associations with sarcopenia were greater in female participants. Conclusion: Autoimmune diagnoses are strongly associated with sarcopenia in 60- to 70-year olds. Variation in specific HLA types and non-coding single nucleotide polymorphisms is also associated with sarcopenia in older carriers free of diagnosed autoimmune diseases. Patients with sarcopenia might benefit from targeted treatment of autoimmune processes.en_US
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.relation.urlhttps://academic.oup.com/biomedgerontology/article-lookup/doi/10.1093/gerona/glz042en_US
dc.rights© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly citeden_US
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectAutoimmuneen_US
dc.subjectInflammationen_US
dc.subjectMuscleen_US
dc.subjectUK Biobanken_US
dc.subjectWessex Classification Subject Headings::Public health. Health statistics. Occupational health. Health educationen_US
dc.titleSarcopenia and Variation in the Human Leukocyte Antigen Complexen_US
dc.typeJournal Articleen_US
dc.identifier.journalThe Journals of Gerontology. Series A, Biological Sciences and Medical Sciencesen_US
dc.identifier.pmcidPMC7176057
dc.description.noteThis article is freely available via NHS OpenAthens. Click on the Publisher URL to access it via the publisher's site.en_US
dc.description.fundingThis work was generously funded by an award to D.M. by the Medical Research Council (http://dx.doi.org/10.13039/501100000265) MR/M023095/1. D.M. and L.C.P. were supported by the University of Exeter Medical School. (http://dx.doi.org/10.13039/501100000737) Input from C.-L.K. and G.K. was supported by the University of Connecticut Health Center http://dx.doi.org/10.13039/100007710). L.F. was supported by the Intramural Research Program of the National Institute on Aging, U.S. National Institutes of Health (http://dx.doi.org/10.13039/100000002). This work was supported by an IPA Assignment Agreement with Dr. Luigi Ferrucci at the National Institute on Aging (http://dx.doi.org/10.13039/100000002) (#20170526)en_US
dc.type.versionPublisheden_US


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© The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited
Except where otherwise noted, this item's license is described as © The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited