Contrasting genetic association of IL2RA with SLE and ANCA-associated vasculitis.
BACKGROUND
Autoimmune diseases are complex and have genetic and environmental susceptibility factors. The objective was to test the genetic association of systemic lupus erythematosus (SLE) and anti-neutrophil cytoplasmic antibody (ANCA) - associated systemic vasculitis (AAV) with SNPs in the IL2RA region and to correlate genotype with serum levels of IL-2RA.


METHODS
Using a cohort of over 700 AAV patients, two SLE case-control studies and an SLE trio collection (totalling over 1000 SLE patients), and a TaqMan genotyping approach, we tested 3 SNPs in the IL2RA locus, rs11594656, rs2104286 & rs41295061, each with a prior association with autoimmune disease; rs11594656 and rs41295061 with type 1 diabetes (T1D) and rs2104286 with multiple sclerosis (MS) and T1D.


RESULTS
We show that SLE is associated with rs11594656 (P = 3.87 x 10-7) and there is some evidence of association of rs41295061 with AAV (P = 0.0122), which both have prior association with T1D. rs2104286, an MS and T1D - associated SNP in the IL2RA locus, is not associated with either SLE or AAV.


CONCLUSIONS
We have confirmed a previous suggestion that the IL2RA locus is associated with SLE and showed some evidence of association with AAV. Soluble IL-2RA concentrations correlate with rs11594656 genotype in quiescent disease in both AAV and SLE. Differential association of autoimmune diseases and SNPs within the IL2RA locus suggests that the IL2RA pathway may prove to play differing, as yet undefined, roles in each disease.
Carr
Edward J
EJ
Cambridge Institute for Medical Research, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0XY, UK. ejc58@cam.ac.uk
Clatworthy
Menna R
MR
Lowe
Christopher E
CE
Todd
John A
JA
Wong
Andrew
A
Vyse
Timothy J
TJ
Kamesh
Lavanya
L
Watts
Richard A
RA
Lyons
Paul A
PA
Smith
Kenneth G C
KG
D000293:Adolescent; D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014657:Vasculitis / Q000097:blood / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
D019268:Antibodies, Antineutrophil Cytoplasmic; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit