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Interleukin 1 polymorphisms in patients with ankylosing spondylitis in Korea.

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 < or = 2 x 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.