A polymorphism within IL21R confers risk for systemic lupus erythematosus.
OBJECTIVE
Interleukin-21 (IL-21) is a member of the type I cytokine superfamily that has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. The expression of IL-21 receptor (IL-21R) is reduced in the B cells of patients with systemic lupus erythematosus (SLE), while serum IL-21 levels are increased both in lupus patients and in some murine lupus models. We recently reported that polymorphisms within the IL21 gene are associated with increased susceptibility to SLE. The aim of this study was to examine the genetic association between single-nucleotide polymorphisms (SNPs) within IL21R and SLE.


METHODS
We genotyped 17 SNPs in the IL21R gene in 2 large cohorts of lupus patients (a European-derived cohort and a Hispanic cohort) and in ethnically matched healthy controls.


RESULTS
We identified and confirmed the association between rs3093301 within the IL21R gene and SLE in the 2 cohorts (meta-analysis odds ratio 1.16 [95% confidence interval 1.08-1.25], P=1.0x10(-4)).


CONCLUSIONS
Our findings indicate that IL21R is a novel susceptibility gene for SLE.
Webb
Ryan
R
Oklahoma Medical Research Foundation, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Merrill
Joan T
JT
Kelly
Jennifer A
JA
Sestak
Andrea
A
Kaufman
Kenneth M
KM
Langefeld
Carl D
CD
Ziegler
Julie
J
Kimberly
Robert P
RP
Edberg
Jeffrey C
JC
Ramsey-Goldman
Rosalind
R
Petri
Michelle
M
Reveille
John D
JD
Alarcón
Graciela S
GS
Vilá
Luis M
LM
Alarcón-Riquelme
Marta E
ME
James
Judith A
JA
Gilkeson
Gary S
GS
Jacob
Chaim O
CO
Moser
Kathy L
KL
Gaffney
Patrick M
PM
Vyse
Timothy J
TJ
Nath
Swapan K
SK
Lipsky
Peter
P
Harley
John B
JB
Sawalha
Amr H
AH
D005260:Female; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino / Q000208:ethnology / Q000235:genetics; D006801:Humans; D053738:Interleukin-21 Receptor alpha Subunit / Q000235:genetics*; D015810:Linkage Disequilibrium / Q000235:genetics; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People / Q000208:ethnology / Q000235:genetics
C508117:IL21R protein, human; D053738:Interleukin-21 Receptor alpha Subunit