HLA B*44
Protective effects in MS susceptibility and MRI outcome measures
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Abstract
Objective: In addition to the main multiple sclerosis (MS) major histocompatibility complex (MHC) risk allele (HLA DRB1*1501), investigations of the MHC have implicated several class I MHC loci (HLA A, HLA B, and HLA C) as potential independent MS susceptibility loci. Here, we evaluate the role of 3 putative protective alleles in MS: HLA A*02, HLA B*44, and HLA C*05.
Methods: Subjects include a clinic-based patient sample with a diagnosis of either MS or a clinically isolated syndrome (n = 532), compared to subjects in a bone marrow donor registry (n = 776). All subjects have 2-digit HLA data. Logistic regression was used to determine the independence of each allele's effect. We used linear regression and an additive model to test for correlation between an allele and MRI and clinical measures of disease course.
Results: After accounting for the effect of HLA DRB1*1501, both HLA A*02 and HLA B*44 are validated as susceptibility alleles (pA*02 0.00039 and pB*44 0.00092) and remain significantly associated with MS susceptibility in the presence of the other allele. Although A*02 is not associated with MS outcome measures, HLA B*44 demonstrates association with a better radiologic outcome both in terms of brain parenchymal fraction and T2 hyperintense lesion volume (p = 0.03 for each outcome).
Conclusion: The MHC class I alleles HLA A*02 and HLA B*44 independently reduce susceptibility to MS, but only HLA B*44 appears to influence disease course, preserving brain volume and reducing the burden of T2 hyperintense lesions in subjects with MS.
Footnotes
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Supplemental data at www.neurology.org
*These authors contributed equally to this work.
Study funding: Supported by the National Multiple Sclerosis Society. P.L.D. is a Harry Weaver Neuroscience Scholar Award Recipient of the National MS Society (NMSS). D.A.H. is a Jacob Javits Scholar of the NIH.
Disclosure: Author disclosures are provided at the end of the article.
Received November 25, 2009. Accepted in final form May 3, 2010.
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Letters: Rapid online correspondence
- HLA B*44: Protective effects in MS susceptibility and MRI outcome measures
- Michael J. Chao, University of Oxford, Department of Clinical Neurology, John Radcliffe Hospital, University of Oxford, Oxford, OX3 9DU.michael.chao@hotmail.co.uk
- Matthew R. Lincoln (Oxford, UK; matthew.lincoln@utoronto.ca), David A. Dyment (Oxford, UK; ddyment@well.ox.ac.uk), Sreeram V. Ramagopalan (Oxford, UK; sramagopalan@gmail.com), George C. Ebers (Oxford, UK; george.ebers@clneuro.ox.ac.uk).
Submitted January 31, 2011 - Reply from the authors
- Philip L. De Jager, Program in Translational NeuroPsychiatric Genomics, Dept of Neurology, Brigham & Women's Hosp, 77 Avenue Louis Pasteur, NRB 168c, Boston, MA 02115pdejager@rics.bwh.harvard.edu
Submitted January 31, 2011
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