|(C;C)||2||1.08x increased risk for multiple sclerosis|
|(C;T)||1.8||0.91x decreased risk for multiple sclerosis|
|(T;T)||2.1||0.70x decreased risk for multiple sclerosis|
The (C) allele of rs6897932, located in the alternatively spliced exon 6 of IL7RA gene and encoding the amino acid threonine rather than isoleucine at amino acid position 244, is associated with a slight increase (18%) in risk of developing multiple sclerosis. [PMID 17660817; Nature Genetics 39, 1083 - 1091 (2007) SG Gregory et al.]
Note that the (C) allele is the most common at this position in all known populations and influences the ratios of the alternative isoforms (membrane bound and soluble) of the gene. Thus, we consider the (T) allele protective.
blog post giving perspective on the significance of this snp
[PMID 17660817] a significant risk factor for multiple sclerosis in four independent (overall P = 2.9 x 10(-7)) influences the amount of soluble and membrane-bound isoforms of the protein by putatively disrupting an exonic splicing silencer.
nejm C allele increasing the risk of multiple sclerosis (odds ratio, approximately 1.2)
[PMID 18721276] A replication case-control study involving 599 Spanish patients with multiple sclerosis yielded a per allele odds ratio of 1.32 per rs6897932(C), (CI: 1.1-1.6, p = 0.0031), and odds per (C;C) genotype vs (T;T) and (C;T) genotypes of 1.5 (CI: 1.18-1.87, p = 0.0007).
|Trait||Type 1 diabetes|
|Title||Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes|
|Odds Ratio||1.12 [1.06-1.19]|
|Title||Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci|
|Odds Ratio||1.12 [1.02-1.23]|
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[PMID 20112030] Genetic variation in the IL7RA/IL7 pathway increases multiple sclerosis susceptibility
[PMID 20952449] Evaluation of the established non-MHC multiple sclerosis loci in an Indian population
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[PMID 17915034] Finding disease candidate genes by liquid association.
[PMID 18354419] IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations.
[PMID 18461312] The immunogenetics of multiple sclerosis.
[PMID 18490360] The complex genetics of multiple sclerosis: pitfalls and prospects.
[PMID 18563381] Study of the association between the CAPSL-IL7R locus and type 1 diabetes.
[PMID 18565446] Refining genetic associations in multiple sclerosis.
[PMID 18853133] Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes.
[PMID 19073967] Shared and distinct genetic variants in type 1 diabetes and celiac disease.
[PMID 19221116] Use of a genetic isolate to identify rare disease variants: C7 on 5p associated with MS.
[PMID 19231135] Variation in the IL7RA and IL2RA genes in German multiple sclerosis patients.
[PMID 19293837] Replication analysis identifies TYK2 as a multiple sclerosis susceptibility factor.
[PMID 19359276] Identification of AF4/FMR2 family, member 3 (AFF3) as a novel rheumatoid arthritis susceptibility locus and confirmation of two further pan-autoimmune susceptibility genes.
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[PMID 19546505] IL-21 drives secondary autoimmunity in patients with multiple sclerosis, following therapeutic lymphocyte depletion with alemtuzumab (Campath-1H).
[PMID 19626040] Follow-up examination of linkage and association to chromosome 1q43 in multiple sclerosis.
[PMID 19956108] Analysis of 55 autoimmune disease and type II diabetes loci: further confirmation of chromosomes 4q27, 12q13.2 and 12q24.13 as type I diabetes loci, and support for a new locus, 12q13.3-q14.1.
[PMID 20007504] Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci.
[PMID 20072139] Association of the AFF3 gene and IL2/IL21 gene region with juvenile idiopathic arthritis.
[PMID 20182566] The genetic aspects of multiple sclerosis.
[PMID 20194581] Interleukin 7 receptor alpha polymorphism rs6897932 and susceptibility to multiple sclerosis in the Western Balkans.
[PMID 20368992] Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients.
[PMID 20405052] The effect of single nucleotide polymorphisms from genome wide association studies in multiple sclerosis on gene expression.
[PMID 21161391] Association between the IL7R T244I polymorphism and multiple sclerosis: a meta-analysis.
[PMID 21244681] Thymic stromal lymphopoietin (TSLP) is associated with allergic rhinitis in children with asthma.
[PMID 21875636] Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination.
[PMID 21911588] IL2RA gene polymorphism rs2104286 A>G seen in multiple sclerosis is associated with intermediate uveitis: possible parallel pathways?
[PMID 22262655] The IL-7Ralpha pathway is quantitatively and functionally altered in CD8 T cells in multiple sclerosis.
|Title||Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.|
|Odds Ratio||1.11 [1.09-1.13]|
[PMID 24166352] The Promoter SNP, but not the Alternative Splicing SNP, is Linked to Multiple Sclerosis Among Jordanian Patients
[PMID 24242875] Interleukin-7 Receptor Single Nucleotide Polymorphism rs6897932 (C/T) and the Susceptibility to Systemic Lupus Erythematosus
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[PMID 24357513] The variant interleukin 1f7 rs3811047 G>A was associated with a decreased risk of gastric cardiac adenocarcinoma in a Chinese Han population
[PMID 22492128] Association of SNPs rs6498169 and rs10984447 with multiple sclerosis in Saudi patients: a model of the usefulness of familial aggregates in identifying genetic linkage in a multifactorial disease.
[PMID 23454692] Concentration and activity of the soluble form of the interleukin-7 receptor alpha in type 1 diabetes identifies an interplay between hyperglycemia and immune function.
[PMID 23462217] Polymorphisms in the interleukin-7 receptor alpha gene and mortality in untreated HIV-infected individuals.
[PMID 23692589] Polymorphism in the interleukin-7 receptor-alpha and outcome after allogeneic hematopoietic cell transplantation with matched unrelated donor.
|Disease||not specified Severe Combined Immune Deficiency|
|CLNDBN||not specified Severe Combined Immune Deficiency|
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[PMID 33568552] U2AF2 binds IL7R exon 6 ectopically and represses its inclusion.