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Coeliac disease-associated polymorphisms influence thymic gene expression

Genes & Immunity volume 15, pages 355–360 (2014)Cite this article

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Abstract

Significant associations between coeliac disease (CD) and single nucleotide polymorphisms (SNPs) distributed over 40 genetic regions have been established. The majority of these SNPs are non-coding and 20 SNPs were, by expression quantitative trait loci (eQTL) analysis, found to harbour cis regulatory potential in peripheral blood mononuclear cells (PBMC). Almost all regions contain genes with an immunological relevant function, of which many act in the same biological pathways. One such pathway is T-cell development in the thymus, a pathway previously not explored in CD pathogenesis. The aim of our study was to explore the regulatory potential of the CD-associated SNPs (n=50) by eQTL analysis in thymic tissue from 42 subjects. In total, 43 nominal significant (P<0.05) eQTLs were found within 24 CD-associated chromosomal regions, corresponding to 27 expression-altering SNPs (eSNPs) and 40 probes (eProbes) that represents 39 unique genes (eGenes). Nine significant probe–SNP pairs (corresponding to 8 eSNPs and 7 eGenes) overlapped with previous findings in PBMC (rs12727642-PARK7, rs296547-DDX59, rs917997-IL18RAP, rs842647-AHSA2, rs13003464-AHSA2, rs6974491-ELMO1, rs2074404-NSF (two independent probes) and rs2298428-UBE2L3). When compared across more tissues, we found that 14 eQTLs could represent potentially novel thymus-specific eQTLs. This implies that CD risk polymorphisms could affect gene regulation in thymus.

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Acknowledgements

We thank Harald Lindberg at Rikshospitalet for collecting the thymus tissues, Siri Flåm and Hege D Sollid for preparing the DNA and RNA samples, and Haleh Saeedi for TaqMan gene expression analyses. This study was supported by grants from the South-Eastern Norway Regional Health Authorities, the Norwegian Diabetes Association and Novo Nordisk.

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Authors and Affiliations

  1. Centre for Immune Regulation, Institute of Immunology, University of Oslo, Oslo University Hospital, Rikshospitalet, Oslo, Norway

    S S Amundsen & L M Sollid

  2. Department of Medical Genetics, University of Oslo, Oslo University Hospital, Ullevål, Oslo, Norway

    M K Viken & B A Lie

  3. Department of Immunology, Oslo University Hospital, Rikshospitalet, Oslo, Norway

    M K Viken & B A Lie

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  1. S S Amundsen
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Correspondence to S S Amundsen.

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Amundsen, S., Viken, M., Sollid, L. et al. Coeliac disease-associated polymorphisms influence thymic gene expression. Genes Immun 15, 355–360 (2014). https://doi.org/10.1038/gene.2014.26

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