Interleukin-7 receptor alpha gene polymorphism influences multiple sclerosis risk in Asians

A recent genome-wide survey identified non–human leukocyte antigen ( HLA ) genes that are related to multiple sclerosis (MS). Among these, an association of a single nucleotide polymorphism (SNP), rs6897932, in the interleukin-7 receptor α gene ( IL-7RA ) with MS susceptibility has been widely replicated in Caucasians.1,–,3 The SNP located in the transmembrane domain of IL-7Rα is nonsynonymous and functional: the MS-susceptible CC allele increases levels of the soluble form of IL-7Rα via exon skipping, and decreases the expression of membrane-bound IL-7Rα, thereby causing decreased IL-7/IL-7R signaling.1,–,3 IL-7/IL-7R signaling induces thymic production of FOXP3+ regulatory T cells, which efficiently ameliorate experimental autoimmune encephalomyelitis,4 an animal model of MS. Thus, the rs6897932 polymorphism of the IL-7RA gene may confer MS susceptibility through decreased production of FOXP3+ regulatory T cells due to downregulated IL-7/IL-7R signaling. This polymorphism has never been reported in either MS or neuromyelitis optica (NMO) in Asians. Therefore, in the present cross-sectional study, we investigated the association of the IL-7RA SNP rs6897932 with non-NMO MS and NMO in the Japanese. ### Methods. All patients with NMO fulfilled the 2006 Wingerchuk5 criteria for NMO, while those with NMO spectrum disorders who did not completely meet the criteria were excluded. All non-NMO patients with MS satisfied …