Interleukin 1 and Nuclear Factor-kB Polymorphisms in Ankylosing Spondylitis in Canada and Korea

TAE-HWAN KIM, MILLICENT A. STONE, PROTON RAHMAN, DAE-HYUN YOO, YONG-WOOK PARK, URSULA PAYNE, DAVE HALLETT, and ROBERT D. INMAN

ABSTRACT.

Objective. The interleukin 1a and 1ß (IL-1a, IL-1ß) are potent mediators of inflammation and immunity. IL-1 receptor antagonist (IL-1Ra) is a protein that binds to IL-1 receptors and competitively inhibits the binding of IL-1a and IL-1ß. There are reports of IL-1 complex gene polymorphisms in ankylosing spondylitis (AS), but the results have been inconsistent. NFKB1 encodes the genes for the p50 and p101 nuclear factor-kB (NF-kB) isoforms, which are recognized as critical to inflammatory disease. To date there have been no reports examining an association between NFKB1 and AS. We investigated polymorphisms of IL-1 complex and NF-kB1 with 2 genetically and geographically different populations.

Methods. Subjects with AS satisfied modified New York criteria for AS. Healthy controls were recruited at each respective site. Subjects with AS were genotyped for the following: IL-1a –889 single nucleotide polymorphism (SNP); IL-1ß +3953 SNP; IL-1Ra (86 base pair variable number tandem repeat within intron 2); and NFKB1 (–94 insertion/deletion polymorphism).

Results. In total, 205 subjects with AS and 200 controls from Seoul, Korea, and 68 subjects with AS and 164 controls from Toronto, Canada, were genotyped for the IL-1a and IL-1ß polymorphisms and 115 controls for the IL-1Ra and NF-kB polymorphisms. There were no differences of IL-1a, IL-1ß, IL-1Ra, and NF-kB polymorphisms between AS patients and controls in these populations.

Conclusion. Our analysis of these SNP in the IL-1 complex and NF-kB genes does not support a major role for either in AS susceptibility in the Seoul and Toronto populations. (J Rheumatol 2005;32:1907-10)

Key Indexing Terms:

INTERLEUKIN 1a
INTERLEUKIN 1ß
RECEPTOR ANTAGONIST

NUCLEAR FACTOR kB
ANKYLOSING SPONDYLITIS

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From the Hospital for Rheumatic Diseases, Hanyang University, Seoul, Korea; St. Michael's Hospital, Toronto, Ontario, Canada; Memorial University of Newfoundland, St. John's, Newfoundland, Canada; and Toronto Western Hospital and Mount Sinai Hospital, University of Toronto, Toronto, Canada.

T-H. Kim, MD, PhD, Assistant Professor; D-H. Yoo, MD, PhD, Professor of Medicine; Y-W. Park, MD, PhD, Clinical Fellow, Hanyang University; M.A. Stone, MD, MSc, Assistant Professor of Medicine, University of Toronto, St. Michael's Hospital; P. Rahman, MD, Associate Professor of Medicine, Memorial University; U. Payne, BSc, Research Associate, Toronto Western Hospital Research Institute; D. Hallett, MSc, Biostatistician, Mount Sinai Hospital, University of Toronto; R.D. Inman, MD, Professor of Medicine, University of Toronto.

Address reprint requests to Dr. R.D. Inman, The Arthritis Center of Excellence, Toronto Western Hospital, ECW 8-005, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada. E-mail: Robert.Inman@uhn.on.ca

Accepted for publication May 30, 2005.

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