PMID- 21288988 OWN - NLM STAT- MEDLINE DCOM- 20110421 LR - 20211020 IS - 1526-632X (Electronic) IS - 0028-3878 (Print) IS - 0028-3878 (Linking) VI - 76 IP - 9 DP - 2011 Mar 1 TI - HLA-DRB1 confers increased risk of pediatric-onset MS in children with acquired demyelination. PG - 781-6 LID - 10.1212/WNL.0b013e31820ee1cd [doi] AB - BACKGROUND: Multiple sclerosis (MS) in the pediatric age group is being increasingly recognized. In adults, complex interactions between genetic and environmental factors contribute to risk and the major genetic component of MS susceptibility localizes to the major histocompatibility complex (human leukocyte antigen [HLA]). Whether HLA alleles predict MS in at-risk children presenting with acquired demyelinating syndromes (ADS) of the CNS is unknown. METHODS: HLA-DRB1 alleles were typed using an allele-specific PCR amplification method on samples from 266 children presenting with ADS enrolled in the prospective Canadian Pediatric Demyelinating Disease Study and from 196 healthy controls. RESULTS: Sixty-four of 266 children with ADS met established criteria for a diagnosis of MS during a mean follow-up of 3.2 +/- 1.5 years. Children harboring DRB1*15 alleles were more likely to be diagnosed with MS (chi(2) = 12.2, p < 0.001; OR = 2.7), an observation strengthened by children of European ancestry (chi(2) = 10.5, p = 0.001; OR = 3.3). DRB1*15 allele frequencies in children with ADS of European ancestry subsequently diagnosed with MS were greater than in children with monophasic ADS (chi(2) = 10.7, p = 0.001) or healthy controls (chi(2) = 12.5, p < 0.001). The proportion of children with non-European ancestry diagnosed with MS was not influenced by DRB1*15 status. CONCLUSION: DRB1*15 alleles confer increased susceptibility to pediatric-onset MS, supporting a fundamental similarity in genetic contribution to MS risk in both pediatric- and adult-onset disease. The specificity of the DRB1*15 risk allele for children with subsequent MS diagnosis, but not for all children with ADS, indicates that the risk conveyed by DRB1*15 relates to chronic CNS disease (MS), rather than acquired demyelination in general. FAU - Disanto, G AU - Disanto G AD - McGill University, Montreal Neurological Institute, Montreal, Quebec, H3A2B4, Canada. FAU - Magalhaes, S AU - Magalhaes S FAU - Handel, A E AU - Handel AE FAU - Morrison, K M AU - Morrison KM FAU - Sadovnick, A D AU - Sadovnick AD FAU - Ebers, G C AU - Ebers GC FAU - Banwell, B AU - Banwell B FAU - Bar-Or, A AU - Bar-Or A CN - Canadian Pediatric Demyelinating Disease Network LA - eng PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't DEP - 20110202 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 0 (HLA-DR Antigens) RN - 0 (HLA-DRB1 Chains) SB - IM CIN - Neurology. 2011 Mar 1;76(9):768-9. PMID: 21288985 MH - Adolescent MH - Age of Onset MH - Alleles MH - Child MH - Child, Preschool MH - Demyelinating Diseases/complications/*epidemiology/*genetics MH - Female MH - Follow-Up Studies MH - *Genetic Predisposition to Disease MH - HLA-DR Antigens/*genetics MH - HLA-DRB1 Chains MH - Humans MH - Infant MH - Longitudinal Studies MH - Male MH - Multiple Sclerosis/complications/*epidemiology/*genetics MH - Mutation MH - Prospective Studies MH - Risk Factors PMC - PMC3053333 FIR - Awuku, Mark IR - Awuku M FIR - Roberts, Louise IR - Roberts L FIR - Baird, J Burke IR - Baird JB FIR - Cacciotti, Nancy IR - Cacciotti N FIR - Banwell, Brenda IR - Banwell B FIR - McGowan, Melissa IR - McGowan M FIR - O'Mahony, Julia IR - O'Mahony J FIR - Ursell, Emily IR - Ursell E FIR - Fairbrother, Courtney IR - Fairbrother C FIR - Kennedy, Julia IR - Kennedy J FIR - Hamilton, Jennifer IR - Hamilton J FIR - Irwin, Samantha IR - Irwin S FIR - Magalhaes, Sandra IR - Magalhaes S FIR - Bhan, Virender IR - Bhan V FIR - Campbell, Trudy IR - Campbell T FIR - Sagar, Lucy IR - Sagar L FIR - Booth, Frances IR - Booth F FIR - Shah, Namrata IR - Shah N FIR - Ann Marrie, Ruth IR - Ann Marrie R FIR - Kupchak, Joan IR - Kupchak J FIR - Buckley, David IR - Buckley D FIR - McGrath, Dianne IR - McGrath D FIR - Penney, Sharon IR - Penney S FIR - Connolly, Mary IR - Connolly M FIR - Kent, Shelia IR - Kent S FIR - Cooper, Pamela IR - Cooper P FIR - Aro, Loris IR - Aro L FIR - Dilenge, Marie-Emmanuelle IR - Dilenge ME FIR - Davies, Heather IR - Davies H FIR - Doja, Asif IR - Doja A FIR - Pohl, Daniela IR - Pohl D FIR - Whiting, Sharon IR - Whiting S FIR - Horth, Chantal IR - Horth C FIR - Ledoux, Sheila IR - Ledoux S FIR - Grand'Maison, Francois IR - Grand'Maison F FIR - Lafreniere, Julie IR - Lafreniere J FIR - Levin, Simon IR - Levin S FIR - Ramu, Mala IR - Ramu M FIR - Lortie, Anne IR - Lortie A FIR - Morin, Sophie IR - Morin S FIR - Breault, Fabiola IR - Breault F FIR - Pellerin, Stephanie IR - Pellerin S FIR - MacDonald, E Athen IR - MacDonald EA FIR - McBride, Vee IR - McBride V FIR - Mah, Jean IR - Mah J FIR - Wright, Caitlin IR - Wright C FIR - Liu, Natarie IR - Liu N FIR - Riddell, Catherine IR - Riddell C FIR - Meaney, Brandon IR - Meaney B FIR - Callen, Dave IR - Callen D FIR - Morgenstern, Leah IR - Morgenstern L FIR - Wyllie, Laurie IR - Wyllie L FIR - Neuman, Heather IR - Neuman H FIR - Meek, David IR - Meek D FIR - Crowell, Alison IR - Crowell A FIR - Lowry, Noel IR - Lowry N FIR - Newmeyer, Doris IR - Newmeyer D FIR - Sebire, Guillaume IR - Sebire G FIR - Houde, Christian IR - Houde C FIR - Wambera, Kati IR - Wambera K FIR - Adams, Colleen IR - Adams C FIR - Robson, Laurie IR - Robson L FIR - Wood, Ellen IR - Wood E FIR - Woolridge, Elaine IR - Woolridge E FIR - Smith, Edythe IR - Smith E FIR - Yager, Jerome IR - Yager J FIR - Berg, Marjorie IR - Berg M FIR - Chick, Hope IR - Chick H FIR - Yim, Conrad IR - Yim C FIR - Montgomery, Leanne IR - Montgomery L EDAT- 2011/02/04 06:00 MHDA- 2011/04/22 06:00 PMCR- 2011/08/26 CRDT- 2011/02/04 06:00 PHST- 2011/02/04 06:00 [entrez] PHST- 2011/02/04 06:00 [pubmed] PHST- 2011/04/22 06:00 [medline] PHST- 2011/08/26 00:00 [pmc-release] AID - WNL.0b013e31820ee1cd [pii] AID - WNL202327 [pii] AID - 10.1212/WNL.0b013e31820ee1cd [doi] PST - ppublish SO - Neurology. 2011 Mar 1;76(9):781-6. doi: 10.1212/WNL.0b013e31820ee1cd. Epub 2011 Feb 2.