Interleukin 1 Polymorphisms in Patients with Ankylosing Spondylitis in Korea

TAE-JONG KIM, TAE-HWAN KIM, HYUN-JOO LEE, LYNETTE PEDDLE, PROTON RAHMAN, PINGZHAO HU, CELIA M.T. GREENWOOD, and ROBERT D. INMAN

ABSTRACT.

Objective. Studies in ankylosing spondylitis (AS) and psoriatic arthritis (PsA) cohorts have demonstrated that the interleukin 1 (IL-1) gene cluster contains a major susceptibility locus for AS and PsA. We examined the association between the IL-1 gene cluster and susceptibility to AS in Korea.

Methods. In total, 451 patients with AS and 402 ethnically matched healthy controls were genotyped with 51 single-nucleotide polymorphisms (SNP) within the IL-1 gene cluster (specifically located within the IL1A, IL1B, IL1RN, and IL1F5-10 genes based on findings of previous association studies). Samples were genotyped by MALDI-TOF mass spectrometry using standard Sequenom iPLEX conditions. Genotyping assays were designed using AssayDESIGNER 2.0 and all SNP designed as 4 multiplex reactions. The resulting product was analyzed using the MassArray Compact Analyzer, and genotype results were determined. Univariate SNP marker distributions in case-control populations were tested by chi-square tests.

Results. No SNP showed association with p value < 0.05. Haplotype analysis revealed an association with the 6 markers (empirical p ≤ 2 ´ 10^-4, corresponding to Bonferroni corrected p = 0.05). Analysis of each 2, 3, 4, 5-marker sliding window revealed association with the IL1A locus (especially haplotype rs12622683-rs11123148-rs10165537).

Conclusion. Single SNP associations noted in outbred Caucasian populations were not found in the Korean AS cohort. Haplotype analysis revealed associations with IL1 locus. These results support the notion that the IL1 locus is associated with susceptibility to AS. (First Release May 15 2008; J Rheumatol 2008;35:1603–8)

Key Indexing Terms:

ANKYLOSING SPONDYLITIS
INTERLEUKIN 1
POLYMORPHISMS
KOREA

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From the Chonnam National University Medical School and Hospital, Gwangju; Hanyang University College of Medicine and Hospital for Rheumatic Diseases, Seoul, Korea; Department of Public Health Sciences, Memorial University of Newfoundland, St. John's, Newfoundland; Program in Genetics and Genomic Biology, Hospital for Sick Children, Toronto; and Toronto Western Hospital and University of Toronto, Toronto, Ontario, Canada.

Supported by the research fund of Hanyang University (HY-2005-I).

T-J. Kim, MD, PhD, Chonnam National University Medical School and Hospital; T-H. Kim, MD, PhD; H-J. Lee, MS, Hanyang University College of Medicine, Hospital for Rheumatic Diseases; L. Peddle, BSc; P. Rahman, MD, FRCPC, Department of Public Health Sciences, Memorial University of Newfoundland; P. Hu, MSc, Biostatistician; C.M.T. Greenwood, PhD, Associate Scientist, Program in Genetics and Genomic Biology, Hospital for Sick Children; R.D. Inman, MD, FRCPC, Toronto Western Hospital and the University of Toronto.

Address reprint requests to Dr. T-H. Kim, Department of Internal Medicine, Division of Rheumatology, The Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul 133-792, Korea. E-mail: thkim@hanyang.ac.kr

Accepted for publication March 4, 2008.

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