Association of IL2RA polymorphisms with susceptibility to multiple sclerosis is not explained by missense mutations in IL2RA.
Genome-wide association studies have identified an association between two intronic single nucleotide polymorphisms (SNPs), rs12722489 and rs2104286, in the interleukin-2 receptor alpha-chain gene (IL2RA) and susceptibility to multiple sclerosis (MS). We studied these SNPs in association with susceptibility to and severity of MS in a population-based cohort of 220 patients from Olmsted County, Minnesota, compared with 442 matched controls. We sequenced the exons, splice sites and 5' and 3' untranslated regions in 27 randomly selected MS patients (powered for allele frequency≥0.04) to search for mutations. No novel missense mutation was identified. Two patients (7.5%) had an exon 2 SNP (rs4308625) and two patients had an exon 4 SNP (rs2228149), both synonymous.
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Marcelo
M
Matiello
Brian G
BG
Weinshenker
Elizabeth J
EJ
Atkinson
Janet
J
Schaefer-Klein
Orhun H
OH
Kantarci
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D004185:Disability Evaluation; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics*; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008910:Minnesota; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D020125:Mutation, Missense; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D022821:RNA Splice Sites; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D022821:RNA Splice Sites