IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production
Name
Maier-2009-IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production.pdf
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Author(s)
Maier, Lisa M.
Lowe, Christopher E.
Cooper, Jason
Downes, Kate
Anderson, David E.
Severson, Christopher
Clark, Pamela M.
Healy, Brian
Walker, Neil
Aubin, Cristin
Date Issued
January 2009
Journal
PLoS Genetics
Publisher
Public Library of Science
Citation
Maier LM, Lowe CE, Cooper J, Downes K, Anderson DE, et al. (2009) IL2RA Genetic Heterogeneity in Multiple Sclerosis and Type 1 Diabetes Susceptibility and Soluble Interleukin-2 Receptor Production. PLoS Genet 5(1): e1000322. doi:10.1371/journal.pgen.1000322
Version
Final published version
Abstract
Multiple sclerosis (MS) and type 1 diabetes (T1D) are organ-specific autoimmune disorders with significant heritability, part of which is conferred by shared alleles. For decades, the Human Leukocyte Antigen (HLA) complex was the only known susceptibility locus for both T1D and MS, but loci outside the HLA complex harboring risk alleles have been discovered and fully replicated. A genome-wide association scan for MS risk genes and candidate gene association studies have previously described the IL2RA gene region as a shared autoimmune locus. In order to investigate whether autoimmunity risk at IL2RA was due to distinct or shared alleles, we performed a genetic association study of three IL2RA variants in a DNA collection of up to 9,407 healthy controls, 2,420 MS, and 6,425 T1D subjects as well as 1,303 MS parent/child trios. Here, we report “allelic heterogeneity” at the IL2RA region between MS and T1D. We observe an allele associated with susceptibility to one disease and risk to the other, an allele that confers susceptibility to both diseases, and an allele that may only confer susceptibility to T1D. In addition, we tested the levels of soluble interleukin-2 receptor (sIL-2RA) in the serum from up to 69 healthy control subjects, 285 MS, and 1,317 T1D subjects. We demonstrate that multiple variants independently correlate with sIL-2RA levels
MIT Department
Broad Institute of MIT and Harvard
Harvard University--MIT Division of Health Sciences and Technology
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DOI of Published Version
http://dx.doi.org/10.1371/journal.pgen.1000322
