Interleukin 7 receptor α chain ( IL7R ) shows allelic and functional association with multiple sclerosis

• DOI: 10.1038/ng2103
• Publication Date: 2007-07-29T13:14:39Z
• Authors: Simon G Gregory; Silke Schmidt; Puneet Seth; Jorge R Oksenberg; John Hart; Angela Prokop; Stacy J Caillier; Maria Ban; An Goris; Lisa F Barcellos; Robin Lincoln; Jacob L McCauley; Stephen J Sawcer; D A S Compston; Benedicte Dubois; Stephen L Hauser; Mariano A Garcia-...; Margaret A Perica...
• Keywords: SNP; Genetic Association; Interleukin-7 receptor

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 alpha 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.