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Variation in IL7R predisposes to sarcoid inflammation

Genes & Immunity volume 10, pages 647–653 (2009)Cite this article

Abstract

Sarcoidosis is a chronic granulomatous disorder characterized by a massive influx of Th1 lymphocytes. Both naive and memory T cells express high levels of interleukin 7 receptor-α (IL7Rα), encoded by the IL7R gene. The purpose of this study was to investigate the role of the IL7R gene region in susceptibility to sarcoidosis. Six common single-nucleotide polymorphisms (SNPs) spanning IL7R were genotyped and analyzed in 475 sarcoidosis patients and 465 healthy controls. Replication of one significant associated SNP was carried out in 206 independent sarcoidosis patients, 127 controls and 126 patients with Löfgren's disease. The rs10213865 SNP was associated with sarcoidosis (P=0.008), and in silico analysis showed a complete linkage (r2=1, D′=1) with a functional nonsynonymous coding SNP in exon 6 (rs6897932, T244I). Combined analysis of 663 individuals with sarcoidosis and 586 controls (homozygous carriers of risk allele, P=5 × 10−4, odds ratio=1.49 (1.19–1.86)) provided strong statistical support for a genuine association of IL7R with the risk of sarcoidosis. In addition, we report the same trend between variation in the IL7R gene and patients with Löfgren's disease, suggesting that variation in IL7R may confer general risk for developing granulomatous lung disease.

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Authors and Affiliations

  1. Department of Pulmonology, Center for Interstitial Lung Diseases, St Antonius Hospital, Nieuwegein, The Netherlands

    M Heron, J C Grutters, C H M van Moorsel & J M M van den Bosch

  2. Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, The Netherlands

    M Heron & A M E Claessen

  3. Department of Clinical Chemistry, St Antonius Hospital, Nieuwegein, The Netherlands

    H J T Ruven

  4. Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands

    T W J Huizinga & A H M van der Helm-van Mil

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  1. M Heron
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Correspondence to J C Grutters.

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Heron, M., Grutters, J., van Moorsel, C. et al. Variation in IL7R predisposes to sarcoid inflammation. Genes Immun 10, 647–653 (2009). https://doi.org/10.1038/gene.2009.55

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