title: Multiple sclerosis-associated single-nucleotide polymorphisms in CLEC16A correlate with reduced SOCS1 and DEXI expression in the thymus.
abstract: Genome-wide association studies have revealed that the 16p13 chromosomal region, including CLEC16A, DEXI, CIITA and SOCS1, is associated with susceptibility to autoimmune diseases. As non-coding single-nucleotide polymorphisms (SNPs) may confer susceptibility to disease by affecting expression of nearby genes, we examined whether autoimmune-associated intronic CLEC16A SNPs (rs12708716, rs6498169 and rs7206912) correlate with the expression of CLEC16A itself as well as neighboring genes in whole-blood and thymic samples. Real-time quantitative PCR analyses show that SOCS1 and DEXI expression was lower in thymic samples carrying at least one of the CLEC16A risk alleles compared with non-carriers of the risk allele. Linear regression analysis revealed a significant correlation between the expression level of CLEC16A and that of SOCS1 and DEXI in thymic samples. These data indicate a possible regulatory role for multiple sclerosis-associated non-coding CLEC16A SNPs and a common control mechanism for the expression of CLEC16A, SOCS1 and DEXI.
authors.affiliation: Department of Neurology, Oslo University Hospital, Oslo, Norway.
authors.forename: I S
authors.initials: IS
authors.lastname: Leikfoss
authors.forename: I-L
authors.initials: IL
authors.lastname: Mero
authors.forename: M K
authors.initials: MK
authors.lastname: Dahle
authors.forename: B A
authors.initials: BA
authors.lastname: Lie
authors.forename: H F
authors.initials: HF
authors.lastname: Harbo
authors.forename: A
authors.initials: A
authors.lastname: Spurkland
authors.forename: T
authors.initials: T
authors.lastname: Berge
mesh_terms: D016022:Case-Control Studies; D002648:Child; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D013950:Thymus Gland / Q000378:metabolism*
chemical_list: C522505:CLEC16A protein, human; C433368:DEXI protein, human; D004268:DNA-Binding Proteins; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009004:Monosaccharide Transport Proteins; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins