title: Cell-specific effects in different immune subsets associated with SOCS1 genotypes in multiple sclerosis.
abstract: BACKGROUND
  Single nucleotide polymorphisms (SNPs) near SOCS1 are associated with multiple sclerosis (MS), but the most important SNPs in the area and mechanisms by which they influence the disease are unknown.
  
  
  METHODS
  A haplotype-tagging association study was performed covering 60.5kbp around SOCS1, and the index SNP was validated in a total of 2292 individuals. mRNA expression of SOCS1 and nearby genes was measured in MS patients with different disease courses and healthy controls. SOCS1 protein expression was studied by flow cytometry in a separate cohort of patients and controls. Differentiation and maturation of monocyte-derived dendritic cells (moDCs) were also studied.
  
  
  RESULTS
  One SNP, rs423674, reached genome-wide significance. No genotype-specific mRNA expression differences were seen, but, by flow cytometry, significant interactions were observed between genotypes for rs423674 and disease activity (relapse or remission) in B cells and regulatory T cells. Furthermore, homozygotes for the risk allele (GG) showed higher levels of CD1a and CD86 than carriers of the protective allele (GT) in immature moDCs and a greater increase of HLA-DR+ cell percentage than GT heterozygotes upon maturation.
  
  
  CONCLUSIONS
  rs423674, or its genetic proxies, may influence MS risk by modulating SOCS1 expression in a cell-specific manner and by influencing dendritic cell function.
authors.affiliation: Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Spain/Achucarro Basque Center for Neuroscience, Spain.
authors.forename: Aitzkoa
authors.initials: A
authors.lastname: Lopez de Lapuente
authors.affiliation: Research Laboratory, Clinical Neurosciences Institute, Hospital Regional Universitario Carlos Haya and Fundación IMABIS.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Pinto-Medel
authors.affiliation: Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Spain/Achucarro Basque Center for Neuroscience, Spain.
authors.forename: Ianire
authors.initials: I
authors.lastname: Astobiza
authors.affiliation: Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Spain/ Achucarro Basque Center for Neuroscience, Spain/ IKERBASQUE, Basque Foundation for Science, Spain.
authors.forename: Iraide
authors.initials: I
authors.lastname: Alloza
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Sunny
authors.initials: S
authors.lastname: Malhotra
authors.affiliation: Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Montalban
authors.affiliation: University of Rostock, Department of Neurology, Germany.
authors.forename: Uwe K
authors.initials: UK
authors.lastname: Zettl
authors.affiliation: Servicio de Neurología, Hospital de Basurto, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Rodríguez-Antigüedad
authors.affiliation: Research Laboratory, Clinical Neurosciences Institute, Hospital Regional Universitario Carlos Haya and Fundación IMABIS.
authors.forename: Oscar
authors.initials: O
authors.lastname: Fernández
authors.affiliation: Neurogenomiks Group, Universidad del País Vasco (UPV/EHU), Spain/ Achucarro Basque Center for Neuroscience, Spain/ IKERBASQUE, Basque Foundation for Science, Spain k.vandenboeck@ikerbasque.org.
authors.forename: Koen
authors.initials: K
authors.lastname: Vandenbroeck
mesh_terms: D000328:Adult; D018949:Antigens, CD1; D001402:B-Lymphocytes / Q000378:metabolism; D051940:B7-2 Antigen; D003713:Dendritic Cells / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D018949:Antigens, CD1; D051940:B7-2 Antigen; C419393:CD1a antigen; D006684:HLA-DR Antigens; D012333:RNA, Messenger; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
keywords: SNP; SOCS1; expression; multiple sclerosis; relapsing–remitting