A polymorphism within IL21R confers risk for systemic lupus erythematosus

Ryan Webb, Joan T. Merrill, Jennifer A. Kelly, Andrea Sestak, Kenneth M. Kaufman, Carl D. Langefeld, Julie Ziegler, Robert P. Kimberly, Jeffrey C. Edberg, Rosalind Ramsey-Goldman, Michelle Petri, John D. Reveille, Graciela S. Alarcón, Luis M. Vilá, Marta E. Alarcón-Riquelme, Judith A. James, Gary S. Gilkeson, Chaim O. Jacob, Kathy L. Moser, Patrick M. GaffneyTimothy J. Vyse, Swapan K. Nath, Peter Lipsky, John B. Harley, Amr H. Sawalha

Research output: Contribution to journalArticle

Abstract

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 = 1.0 × 10 -4). Conclusion. Our findings indicate that IL21R is a novel susceptibility gene for SLE.

Original languageEnglish (US)
Pages (from-to)2402-2407
Number of pages6
JournalArthritis and Rheumatism
Volume60
Issue number8
DOIs
StatePublished - Aug 2009

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Interleukin-21 Receptors
Systemic Lupus Erythematosus
Genes
Single Nucleotide Polymorphism
B-Lymphocytes
Plasma Cells
Hispanic Americans
Meta-Analysis
Immunoglobulins
Cell Differentiation
Immune System
Cohort Studies
Odds Ratio
Confidence Intervals
Cytokines
Serum

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Webb, R., Merrill, J. T., Kelly, J. A., Sestak, A., Kaufman, K. M., Langefeld, C. D., ... Sawalha, A. H. (2009). A polymorphism within IL21R confers risk for systemic lupus erythematosus. Arthritis and Rheumatism, 60(8), 2402-2407. https://doi.org/10.1002/art.24658

A polymorphism within IL21R confers risk for systemic lupus erythematosus. / Webb, Ryan; Merrill, Joan T.; Kelly, Jennifer A.; Sestak, Andrea; Kaufman, Kenneth M.; Langefeld, Carl D.; Ziegler, Julie; Kimberly, Robert P.; Edberg, Jeffrey C.; Ramsey-Goldman, Rosalind; Petri, Michelle; Reveille, John D.; Alarcón, Graciela S.; Vilá, Luis M.; Alarcón-Riquelme, Marta E.; James, Judith A.; Gilkeson, Gary S.; Jacob, Chaim O.; Moser, Kathy L.; Gaffney, Patrick M.; Vyse, Timothy J.; Nath, Swapan K.; Lipsky, Peter; Harley, John B.; Sawalha, Amr H.

In: Arthritis and Rheumatism, Vol. 60, No. 8, 08.2009, p. 2402-2407.

Research output: Contribution to journalArticle

Webb, R, Merrill, JT, Kelly, JA, Sestak, A, Kaufman, KM, Langefeld, CD, Ziegler, J, Kimberly, RP, Edberg, JC, Ramsey-Goldman, R, Petri, M, Reveille, JD, Alarcón, GS, Vilá, LM, Alarcón-Riquelme, ME, James, JA, Gilkeson, GS, Jacob, CO, Moser, KL, Gaffney, PM, Vyse, TJ, Nath, SK, Lipsky, P, Harley, JB & Sawalha, AH 2009, 'A polymorphism within IL21R confers risk for systemic lupus erythematosus', Arthritis and Rheumatism, vol. 60, no. 8, pp. 2402-2407. https://doi.org/10.1002/art.24658
Webb R, Merrill JT, Kelly JA, Sestak A, Kaufman KM, Langefeld CD et al. A polymorphism within IL21R confers risk for systemic lupus erythematosus. Arthritis and Rheumatism. 2009 Aug;60(8):2402-2407. https://doi.org/10.1002/art.24658
Webb, Ryan ; Merrill, Joan T. ; Kelly, Jennifer A. ; Sestak, Andrea ; Kaufman, Kenneth M. ; Langefeld, Carl D. ; Ziegler, Julie ; Kimberly, Robert P. ; Edberg, Jeffrey C. ; Ramsey-Goldman, Rosalind ; Petri, Michelle ; Reveille, John D. ; Alarcón, Graciela S. ; Vilá, Luis M. ; Alarcón-Riquelme, Marta E. ; James, Judith A. ; Gilkeson, Gary S. ; Jacob, Chaim O. ; Moser, Kathy L. ; Gaffney, Patrick M. ; Vyse, Timothy J. ; Nath, Swapan K. ; Lipsky, Peter ; Harley, John B. ; Sawalha, Amr H. / A polymorphism within IL21R confers risk for systemic lupus erythematosus. In: Arthritis and Rheumatism. 2009 ; Vol. 60, No. 8. pp. 2402-2407.
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T1 - A polymorphism within IL21R confers risk for systemic lupus erythematosus

AU - Webb, Ryan

AU - Merrill, Joan T.

AU - Kelly, Jennifer A.

AU - Sestak, Andrea

AU - Kaufman, Kenneth M.

AU - Langefeld, Carl D.

AU - Ziegler, Julie

AU - Kimberly, Robert P.

AU - Edberg, Jeffrey C.

AU - Ramsey-Goldman, Rosalind

AU - Petri, Michelle

AU - Reveille, John D.

AU - Alarcón, Graciela S.

AU - Vilá, Luis M.

AU - Alarcón-Riquelme, Marta E.

AU - James, Judith A.

AU - Gilkeson, Gary S.

AU - Jacob, Chaim O.

AU - Moser, Kathy L.

AU - Gaffney, Patrick M.

AU - Vyse, Timothy J.

AU - Nath, Swapan K.

AU - Lipsky, Peter

AU - Harley, John B.

AU - Sawalha, Amr H.

PY - 2009/8

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N2 - 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 = 1.0 × 10 -4). Conclusion. Our findings indicate that IL21R is a novel susceptibility gene for SLE.

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