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Multiple sclerosis-associated single-nucleotide polymorphisms in CLEC16A correlate with reduced SOCS1 and DEXI expression in the thymus

Genes & Immunity volume 14, pages 62–66 (2013)Cite this article

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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.

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Acknowledgements

This study was funded by grants from The South-Eastern Norway Regional Health Authority, Ullevål University Hospital Scientific Advisory Council (VIRUUS), Biogen Idec Norway AS, The Norwegian Diabetes Association and the Odd Fellow society. We would like to thank Harald Lindeberg and the Norwegian Bone Marrow Registry for providing samples; Marte Viken, Siri Flåm, Hege D Sollid and Hanne Sæther for collecting and preparing the RNA samples; and Christian Page for help with statistical analyses.

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Authors and Affiliations

  1. Department of Neurology, Oslo University Hospital, Oslo, Norway

    I S Leikfoss, I-L Mero, H F Harbo & T Berge

  2. Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

    I S Leikfoss, M K Dahle, A Spurkland & T Berge

  3. Department of Medical Genetics, University of Oslo and Oslo University Hospital, Oslo, Norway

    I-L Mero & B A Lie

  4. Institute of Clinical Medicine, University of Oslo, Oslo, Norway

    H F Harbo

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  1. I S Leikfoss
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Correspondence to T Berge.

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Competing interests

Inger-Lise Mero has received an unrestricted grant for running expenses in this project from Biogen Idec Norway AS.

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Leikfoss, I., Mero, IL., Dahle, M. et al. Multiple sclerosis-associated single-nucleotide polymorphisms in CLEC16A correlate with reduced SOCS1 and DEXI expression in the thymus. Genes Immun 14, 62–66 (2013). https://doi.org/10.1038/gene.2012.52

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