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Genetic risk factors for pediatric-onset multiple sclerosis.
Gianfrancesco, Milena A; Stridh, Pernilla; Shao, Xiaorong; Rhead, Brooke; Graves, Jennifer S; Chitnis, Tanuja; Waldman, Amy; Lotze, Timothy; Schreiner, Teri; Belman, Anita; Greenberg, Benjamin; Weinstock-Guttman, Bianca; Aaen, Gregory; Tillema, Jan M; Hart, Janace; Caillier, Stacy; Ness, Jayne; Harris, Yolanda; Rubin, Jennifer; Candee, Meghan; Krupp, Lauren; Gorman, Mark; Benson, Leslie; Rodriguez, Moses; Mar, Soe; Kahn, Ilana; Rose, John; Roalstad, Shelly; Casper, T Charles; Shen, Ling; Quach, Hong; Quach, Diana; Hillert, Jan; Hedstrom, Anna; Olsson, Tomas; Kockum, Ingrid; Alfredsson, Lars; Schaefer, Catherine; Barcellos, Lisa F; Waubant, Emmanuelle.
Afiliação
  • Gianfrancesco MA; Division of Epidemiology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
  • Stridh P; Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
  • Shao X; Division of Epidemiology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
  • Rhead B; Computational Biology Graduate Group, University of California, Berkeley, Berkeley, CA, USA.
  • Graves JS; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
  • Chitnis T; Partners Pediatric Multiple Sclerosis Center, Massachusetts General Hospital for Children, Boston, MA, USA.
  • Waldman A; Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Lotze T; Blue Bird Circle Multiple Sclerosis Center, Baylor College of Medicine, Houston, TX, USA.
  • Schreiner T; Children's Hospital Colorado, University of Colorado, Denver, CO, USA.
  • Belman A; The Lourie Center for Pediatric MS, Stony Brook Children's Hospital, Stony Brook, NY, USA.
  • Greenberg B; Department of Neurology & Neurotherapeutics, University of Texas Southwestern, Dallas, TX, USA.
  • Weinstock-Guttman B; Pediatric Multiple Sclerosis Center, Jacobs Neurological Institute, SUNY Buffalo, Buffalo, NY, USA.
  • Aaen G; Pediatric MS Center, Loma Linda University Children's Hospital, Loma Linda, CA, USA.
  • Tillema JM; Pediatric MS Center, Mayo Clinic, Rochester, MN, USA.
  • Hart J; Department of Neurology and Regional Pediatric MS Center, University of California, San Francisco, San Francisco, CA, USA.
  • Caillier S; Department of Neurology and Regional Pediatric MS Center, University of California, San Francisco, San Francisco, CA, USA.
  • Ness J; Center for Pediatric Onset Demyelinating Disease, University of Alabama and Children's Hospital of Alabama, Birmingham, AL, USA.
  • Harris Y; Center for Pediatric Onset Demyelinating Disease, University of Alabama and Children's Hospital of Alabama, Birmingham, AL, USA.
  • Rubin J; Division of Neurology, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
  • Candee M; University of Utah and Primary Children's Hospital, Salt Lake City, UT, USA.
  • Krupp L; The Lourie Center for Pediatric MS, Stony Brook Children's Hospital, Stony Brook, NY, USA.
  • Gorman M; Boston Children's Hospital, Boston, MA, USA.
  • Benson L; Boston Children's Hospital, Boston, MA, USA.
  • Rodriguez M; Pediatric MS Center, Mayo Clinic, Rochester, MN, USA.
  • Mar S; Pediatric-onset Demyelinating Diseases and Autoimmune Encephalitis Center, St. Louis Children's Hospital, Washington University School of Medicine, St. Louis, MO, USA.
  • Kahn I; Children's National Medical Center, Washington, DC, USA.
  • Rose J; Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Roalstad S; Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Casper TC; Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT, USA.
  • Shen L; Division of Research, Kaiser Permanente, Oakland, CA, USA.
  • Quach H; Division of Epidemiology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
  • Quach D; Division of Epidemiology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.
  • Hillert J; Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.
  • Hedstrom A; Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden.
  • Olsson T; Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
  • Kockum I; Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
  • Alfredsson L; Institute of Environmental Medicine (IMM), Karolinska Institutet, Stockholm, Sweden/Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden.
  • Schaefer C; Division of Research, Kaiser Permanente, Oakland, CA, USA/Research Program on Genes, Environment and Health, Kaiser Permanente, Oakland, CA.
  • Barcellos LF; Division of Epidemiology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA/Computational Biology Graduate Group, University of California, Berkeley, Berkeley, CA, USA; Division of Research, Kaiser Permanente, Oakland, CA, USA.
  • Waubant E; Department of Neurology, University of California, San Francisco, San Francisco, CA, USA.
Mult Scler ; 24(14): 1825-1834, 2018 12.
Article em En | MEDLINE | ID: mdl-28980494
ABSTRACT

BACKGROUND:

Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology.

OBJECTIVE:

We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to POMS.

METHODS:

Cases with onset <18 years (n = 569) and controls (n = 16,251) were included from the United States and Sweden. Adjusted logistic regression and meta-analyses were performed for individual risk variants and a weighted genetic risk score (wGRS) for non-MHC variants. Results were compared to adult MS cases (n = 7588).

RESULTS:

HLA-DRB1*1501 was strongly associated with POMS (odds ratio (OR)meta = 2.95, p < 2.0 × 10-16). Furthermore, 28 of 104 non-MHC variants studied (23%) were associated (p < 0.05); POMS cases carried, on average, a higher burden of these 28 variants compared to adults (ORavg = 1.24 vs 1.13, respectively), though the difference was not significant. The wGRS was strongly associated with POMS (ORmeta = 2.77, 95% confidence interval 2.33, 3.32, p < 2.0 × 10-16) and higher, on average, when compared to adult cases. Additional class III risk variants in the MHC region associated with POMS were revealed after accounting for HLA-DRB1*1501 and HLA-A*02.

CONCLUSION:

Pediatric and adult MS share many genetic variants suggesting similar biological processes are present. MHC variants beyond HLA-DRB1*1501 and HLA-A*02 are also associated with POMS.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Cadeias HLA-DRB1 / Esclerose Múltipla Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male País como assunto: Europa Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Predisposição Genética para Doença / Polimorfismo de Nucleotídeo Único / Cadeias HLA-DRB1 / Esclerose Múltipla Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male País como assunto: Europa Idioma: En Ano de publicação: 2018 Tipo de documento: Article