IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations

Abstract

Multiple sclerosis (MS) is the most common chronic inflammatory neurologic disorder diagnosed in young adults and, due to its chronic course, is responsible for a substantial economic burden. MS is considered to be a multifactorial disease in which both genetic and environmental factors intervene. The well-established human leukocyte antigen (HLA) association does not completely explain the genetic impact on disease susceptibility. However, identification and validation of non-HLA-genes conferring susceptibility to MS has proven to be difficult probably because of the small individual contribution of each of these genes. Recently, associations with two single nucleotide polymorphisms (SNPs) in the IL2RA gene (rs12722489, rs2104286) and one SNP in the IL7RA gene (rs6897932) have been reported by several groups. These three SNPs were genotyped in a French and a German population of MS patients using the hME assay by the matrix-assisted laser desorption/ionization time of flight technology (Sequenom, San Diego, CA, USA). We show that these SNPs do contribute to the risk of MS in these two unrelated European MS patient populations with odds ratios varying from 1.1 to 1.5. The discovery and validation of new genetic risk factors in independent populations may help toward the understanding of MS pathogenesis by providing valuable information on biological pathways to be investigated.

Replication of KIAA0350, IL2RA, RPL5 and CD58 as multiple sclerosis susceptibility genes in Australians

“…Although rs12722489 was significantly associated with risk in a recent validation study conducted in over 600 Canadian MS families, 10 it showed only marginal association (P ¼ 0.065) with risk in a combined French and German sample. 8 We did not genotype rs1570538, which was associated with risk in Spanish MS patients. 9 Located in intron 6 of the RPL5 (ribosomal protein L5) gene on chromosome 1p22, rs6604026 was associated with the risk of MS (P ¼ 0.…”

“…Recently the International MS Genetics Consortium (IMSGC) published the first SNP-based GWAS for MS with the aim of identifying novel MS susceptibility genes, and a list of 17 SNPs in 13 different gene loci were reported as showing statistical evidence (P ¼ 6 Â 10 À3 to P ¼ 9 Â 10 À81 ) of association with disease susceptibility. 5 Replication studies have since been performed, and provide support for a causal link between variation in the interleukin 7 receptor (IL7R), [6][7][8] interleukin 2 receptor alpha (IL2RA, also known as CD25), [8][9][10] EV15 11 and disease pathogenesis.…”

Multiple sclerosis genetics

“…These loci (the first non-MHC loci that were definitely associated with MS risk) encoded genes involved in immune regulation: the interleukin-2 receptor (IL2Ra) and the interleukin-7 receptor (IL7Ra). Associations with MS susceptibility for both loci were subsequently validated in other populations (Matesanz et al, 2001;Gregory et al, 2007;Lundmark et al, 2007a, b;Rubio et al, 2008;Weber et al, 2008). This landmark achievement established, unquestionably, that genes outside the MHC contributed to MS susceptibility.…”

RGMA and IL21R show association with experimental inflammation and multiple sclerosis

“…5,6 Only recently, with analysis of very large cohorts, non-human leukocyte antigen MS genes are starting to be unambiguously identified. [7][8][9][10][11][12][13][14] Another important concept is the sharing of risk genes between inflammatory diseases, 15 as now demonstrated for type 1 diabetes and MS genes. 12 Therefore, cross-disciplinary genetics may be rewarding.…”