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An IL7RA exon 5 polymorphism is associated with impaired IL-7Rα splicing and protection against tuberculosis in Ghana

Genes & Immunity volume 20, pages 514–519 (2019)Cite this article

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Abstract

Functional interleukin-7 receptor α-chain (IL-7Rα) genetic variants, which affect alternative splicing and expression of the soluble IL-7Rα, are associated with susceptibility to autoimmunity. We previously described aberrant IL-7Rα expression and impaired IL-7-mediated T-cell functions in tuberculosis patients. In the present study, we investigated a possible role of IL7RA gene variants. Six exonic IL7RA polymorphisms were genotyped and two minor alleles were found at lower frequencies in tuberculosis patients as compared to healthy contacts from Ghana (rs11567764, p = 0.002; rs1494558, p = 0.01). The rs11567764 polymorphism tags an IL7RA haplotype exclusively found in African populations and was predicted to affect splicing of exon 5. Reduced mRNA expression of the Δexon_5-6 variant was found in T-cells from carriers of the protective rs11567764 allele. Although we were not able to demonstrate the causative effect of rs11567764, our findings suggested functional implications of genetic variants on IL-7Rα splicing and with potential impact on T-cell protection against tuberculosis.

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Acknowledgements

We gratefully thank all donors for participating in this study.

Funding

The study was supported by the German Research Foundation (DFG, JA 1479/5-1) and the German Leprosy and TB relief association (DAHW) project: TB Biomarkers to MJ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of General Pediatrics, Neonatology, and Pediatric Cardiology, Medical Faculty, University Children’s Hospital, Duesseldorf, Germany

    Christian Lundtoft, Alptekin Güler, Kirstin Harling, Ertan Mayatepek, Norman Nausch & Marc Jacobsen

  2. Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, Ghana

    Anthony Afum-Adjei Awuah, Richard O. Phillips & Ellis Owusu-Dabo

  3. School of Medical Sciences, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana

    Anthony Afum-Adjei Awuah & Richard O. Phillips

  4. Institute of Virology, University Hospital Duesseldorf, Heinrich Heine University, Duesseldorf, Germany

    Heiner Schaal

  5. School of Public Health, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana

    Ellis Owusu-Dabo

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  1. Christian Lundtoft
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Correspondence to Marc Jacobsen.

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Lundtoft, C., Awuah, A.AA., Güler, A. et al. An IL7RA exon 5 polymorphism is associated with impaired IL-7Rα splicing and protection against tuberculosis in Ghana. Genes Immun 20, 514–519 (2019). https://doi.org/10.1038/s41435-018-0049-5

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  • DOI: https://doi.org/10.1038/s41435-018-0049-5

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