title: Multiple Sclerosis Risk Allele in CLEC16A Acts as an Expression Quantitative Trait Locus for CLEC16A and SOCS1 in CD4+ T Cells.
abstract: For multiple sclerosis, genome wide association studies and follow up studies have identified susceptibility single nucleotide polymorphisms located in or near CLEC16A at chromosome 16p13.13, encompassing among others CIITA, DEXI and SOCS1 in addition to CLEC16A. These genetic variants are located in intronic or intergenic regions and display strong linkage disequilibrium with each other, complicating the understanding of their functional contribution and the identification of the direct causal variant(s). Previous studies have shown that multiple sclerosis-associated risk variants in CLEC16A act as expression quantitative trait loci for CLEC16A itself in human pancreatic β-cells, for DEXI and SOCS1 in thymic tissue samples, and for DEXI in monocytes and lymphoblastoid cell lines. Since T cells are major players in multiple sclerosis pathogenesis, we have performed expression analyses of the CIITA-DEXI-CLEC16A-SOCS1 gene cluster in CD4+ and CD8+ T cells isolated from multiple sclerosis patients and healthy controls. We observed a higher expression of SOCS1 and CLEC16A in CD4+ T cells in samples homozygous for the risk allele of CLEC16A rs12927355. Pair-wise linear regression analysis revealed high correlation in gene expression in peripheral T cells of CIITA, DEXI, CLEC16A and SOCS1. Our data imply a possible regulatory role for the multiple sclerosis-associated rs12927355 in CLEC16A.
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ingvild S
authors.initials: IS
authors.lastname: Leikfoss
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Pankaj K
authors.initials: PK
authors.lastname: Keshari
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Marte W
authors.initials: MW
authors.lastname: Gustavsen
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Anja
authors.initials: A
authors.lastname: Bjølgerud
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ina S
authors.initials: IS
authors.lastname: Brorson
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Elisabeth G
authors.initials: EG
authors.lastname: Celius
authors.affiliation: Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
authors.forename: Anne
authors.initials: A
authors.lastname: Spurkland
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Steffan D
authors.initials: SD
authors.lastname: Bos
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Hanne F
authors.initials: HF
authors.lastname: Harbo
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors.forename: Tone
authors.initials: T
authors.lastname: Berge
mesh_terms: D000328:Adult; D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009103:Multiple Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012307:Risk Factors; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics* / Q000378:metabolism; D055815:Young Adult
chemical_list: C522505:CLEC16A protein, human; D037181:Lectins, C-Type; D009004:Monosaccharide Transport Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins