Interleukin 7 receptor a chain (IL7R) shows allelic and functional association with multiple sclerosis
Interleukin 7 receptor a chain (IL7R) shows allelic and functional association with multiple sclerosis
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DOI：
10.1038/ng2103
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发表时间：
2007-09-01
期刊：
影响因子：
30.8
通讯作者：
Haines, Jonathan L.
中科院分区：
文献类型：
--
作者：
Gregory, Simon G.;Schmidt, Silke;Haines, Jonathan L.
多发性硬化症是一种具有很强遗传成分的脱髓鞘神经退行性疾病。先前的遗传风险研究未能识别 6p 染色体上主要组织相容性复合体之外的一致连锁区域或基因。我们在四个独立的基于家庭或病例对照数据集中描述了编码白细胞介素7受体α链（IL7R）的基因中多态性的等位基因关联作为多发性硬化症的显着危险因素（总体P 2.9 x 10(-7)）。此外，可能的因果 SNP rs6897932 位于 IL7R 的可变剪接外显子 6 内，对基因表达具有功能性影响。 SNP 通过破坏外显子剪接沉默子来影响蛋白质的可溶性和膜结合亚型的数量。
Multiple sclerosis is a demyelinating neurodegenerative disease with a strong genetic component. Previous genetic risk studies have failed to identify consistently linked regions or genes outside of the major histocompatibility complex on chromosome 6p. We describe allelic association of a polymorphism in the gene encoding the interleukin 7 receptor a chain ( IL7R) as a significant risk factor for multiple sclerosis in four independent family- based or case- control data sets ( overall P 2.9 x 10(-7)). Further, the likely causal SNP, rs6897932, located within the alternatively spliced exon 6 of IL7R, has a functional effect on gene expression. The SNP influences the amount of soluble and membrane- bound isoforms of the protein by putatively disrupting an exonic splicing silencer.