Single nucleotide polymorphisms of the interleukin-33 (IL-33) gene are associated with ankylosing spondylitis in Chinese individuals: a case-control pilot study

OBJECTIVES: Previous studies have found that serum levels of interleukin (IL)-33 are elevated in patients with ankylosing spondylitis (AS). The aim of this study was to determine whether the single nucleotide polymorphisms (SNPs) in the IL-33 gene are associated with susceptibility to AS in a Chinese population.

METHOD: Eight SNPs in the IL-33 gene (rs1891385, rs16924144, rs2210463, rs16924159, rs10118795, rs1929992, rs10975519, and rs1048274) were genotyped by the improved multiplex ligase detection reaction (iMLDR) method in 400 patients with AS and 395 geographically and ethnically matched healthy controls. Haplotypes were constructed after linkage disequilibrium (LD) analysis.

RESULTS: There were statistically significant differences at SNPs rs1891385, rs2210463, rs10118795, rs1929992, rs10975519, and rs1048274 in the IL-33 gene between cases and controls. The A allele frequency of rs1891385 was lower in the patient group than in the controls [odds ratio (OR) 0.762] whereas the A allele frequency of rs2210463 and the C allele frequency of rs10118795 and rs1929992 were higher in the patient group than in the controls (OR 1.265, 1.305, and 1.248, respectively). However, there were no differences in the genotype distribution and allele frequencies of rs16924144 and rs16924159 between the patients and controls (p > 0.05). Four SNPs (rs10118795, rs1929992, rs10975519, and rs1048274) were in strong LD and were included in four haplotypes: ht1 (CCCG), ht2 (CCTA), ht3 (CTCG), and ht4 (TTCG). Haplotype ht4 was associated with a decreased risk of AS [OR 0.766, 95% confidence interval (CI) 0.626-0.937, χ(2) = 6.761, p = 0.009].

CONCLUSIONS: The results suggest that SNPs and the TTCG haplotype of the IL-33 gene are associated with the development of AS in a Chinese Han population.