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Analysis of HLA-DRB3 alleles and supertypical genotypes in the MHC Class II region in sporadic inclusion body myositis
Authors:Arada Rojana-udomsart  Chalermchai Mitrpant  Ian James  Campbell Witt  Merrilee Needham  Timothy Day  Lynette Kiers  Alastair Corbett  Patricia Martinez  Steve D. Wilton  Frank L. Mastaglia
Affiliation:1. Australian Neuro-muscular Research Institute and Centre for Neuromuscular and Neurological disorders, The University of Western Australia, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia;2. Department of Medicine, Yala Hospital, Yala, Thailand;3. Department of Biochemistry, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand;4. Centre for Clinical Immunology & Biomedical Statistics, Institute for Immunology & Infectious Diseases, Murdoch University & Royal Perth Hospital, Western Australia, Australia;5. Department of Clinical Immunology, PathWest, Laboratory Medicine, Royal Perth Hospital, Perth, Western Australia, Australia;6. Department of Neurology, Royal North Shore Hospital, St Leonards, NSW, Australia;7. Department of Medicine, Northern Clinical School, University of Sydney, Sydney, NSW, Australia;8. Department of Neurology & Neurophysiology, Royal Melbourne Hospital, Parkville, Victoria, Australia;9. Department of Medicine, University of Melbourne, Parkville, Victoria, Australia;10. Department of Neurology, Concord Hospital, Concord, NSW, Australia;1. Neurogenetic Clinic, Department of Neurology, Schneider Children''s Medical Center of Israel, Petah Tiqwa, Affiliated with Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel;2. Pediatric Neurology and Child Development Center, Hillel Yaffe Medical Center, Hadera, Affiliated with Rappaport Faculty of Medicine, Technion—Israel Institute of Technology, Haifa, Israel;3. Department of Pathology, Hadassah University Hospital, Hebrew University-Hadassah Medical School, Jerusalem, Israel;4. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université de Strasbourg, et Collège de France, 67404 Illkirch, France;1. Division of Clinical and Metabolic Genetics, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada;2. Division of Pediatric Neurology, Montreal Children''s Hospital-McGill University Health Center, Montreal, Canada;3. Division of Pediatric Neurology, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia;4. Division of Neurology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada;5. Department of Clinical Dietetics, University of Toronto, The Hospital for Sick Children, Toronto, Canada;6. Department of Psychology, University of Toronto, The Hospital for Sick Children, Toronto, Canada;7. Genetics and Genome Biology Research Program, Research Institute, The Hospital for Sick Children, Toronto, Canada;1. Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA, United States;2. Molecular and Cellular Neuroscience Department, The Scripps Research Institute, La Jolla, CA 92037, United States;3. Genetics Department, The Scripps Research Institute, La Jolla, CA, United States;1. Ophthalmological Unit, Department of Clinical Sciences and Community Health, Ca'' Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy;2. Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, Melbourne, Australia;3. Department of Ophthalmology, University of Bonn, Bonn, Germany;4. Rare Diseases Center, Department of Clinical Sciences and Community Health, Ca'' Granda Foundation-Ospedale Maggiore Policlinico, University of Milan, Milan, Italy;1. Division of Neurology, Department of Pediatrics, Queen Sirikit National Institute of Child Health, Ministry of Public Health, College of Medicine, Rangsit University, Bangkok, Thailand;2. Department of Pediatrics, Maharat Nakhon Ratchasima Hospital, Nakhon Ratchasima, Thailand;3. Department of Pediatrics, Ratchaburi Hospital, Ratchaburi, Thailand;4. Department of Pediatrics, Udon Thani Hospital, Udon Thani, Thailand;5. Center for Medical Genomics, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand;6. Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
Abstract:We compared the carriage frequencies of HLA-DRB3 and its major alleles and of HLA-DRB4 and HLA-DRB5 in an Australian sIBM cohort and a population control group who had previously been genotyped for the HLA-DRB1*03:01 risk allele. There was a strong disease association with the carriage of the DRB3*01:01 allele which was accounted for by its linkage disequilibrium with DRB1*03:01. The carriage of HLA-DRB4 was found to be strongly protective and abrogated the risk effect of HLA-DRB1*03:01. The findings indicate that haplotypic combinations of alleles at the HLA-DRB1 and secondary HLA-DRB loci have important risk modifying effects in sIBM.
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