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

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An IL7RA exon 5 polymorphism is associated with impaired IL-7Rα splicing and protection against tuberculosis in Ghana.
Genes and Immunity ( IF 5.0 ) Pub Date : 2018-10-31 , DOI: 10.1038/s41435-018-0049-5
Christian Lundtoft ₁ , Anthony Afum-Adjei Awuah _{2,

3} , Alptekin Güler ₁ , Kirstin Harling ₁ , Heiner Schaal ₄ , Ertan Mayatepek ₁ , Richard O Phillips _{2,

3} , Norman Nausch ₁ , Ellis Owusu-Dabo _{2,

5} , Marc Jacobsen ₁

Affiliation

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.

中文翻译：

IL7RA 外显子 5 多态性与受损的 IL-7Rα 剪接和对加纳结核病的保护有关。

影响可溶性 IL-7Rα 可变剪接和表达的功能性白细胞介素 7 受体 α 链 (IL-7Rα) 遗传变异与自身免疫的易感性有关。我们之前描述了结核病患者中异常的 IL-7Rα 表达和 IL-7 介导的 T 细胞功能受损。在本研究中，我们研究了 IL7RA 基因变体的可能作用。与来自加纳的健康接触者相比，对六个外显子 IL7RA 多态性进行了基因分型，并且在结核病患者中发现两个次要等位基因的频率较低（rs11567764，p = 0.002；rs1494558，p = 0.01）。rs11567764 多态性标记了一种仅在非洲人群中发现的 IL7RA 单倍型，预计会影响外显子 5 的剪接。在来自保护性 rs11567764 等位基因携带者的 T 细胞中发现 Δexon_5-6 变体的 mRNA 表达降低。尽管我们无法证明 rs11567764 的致病作用，但我们的研究结果表明遗传变异对 IL-7Rα 剪接的功能影响以及对 T 细胞抗结核病保护的潜在影响。

更新日期：2018-10-31

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