| Objective: The aim of this study was to examine whether the single nucleotide polymorphisms(SNPs) in the IL-33 gene are associated with susceptibility to ankylosing spondylitis(AS).Methods: Eight SNPs(rs1891385, rs16924144, rs2210463, rs16924159, rs10118795, rs1929992, rs10975519, rs1048274) were genotyped in 400 AS patients and 395 sex-, age- and ethnically matched healthy controls using the improved Multi-ligase detection reaction(i MLDR). All AS patients were recruited from the Department of Rheumatology and Immunology, the First Affiliated Hospital of Anhui Medical University, and fulfilled the 1984 modified New York criteria. All control population consisted of unrelated healthy individuals from the same geographical regions. The analysis was performed between AS patients and healthy controls for genotype, allele, homozygote, dominant model and recessive model, respectively. Haplotypes were constructed after linkage disequilibrium(LD) analysis. Patients’ functional impairment and disease activity were measured by the Bath Ankylosing Spondylitis Functional Index(BASFI) and the Bath Ankylosing Spondylitis Disease Activity Index(BASDAI), respectively. Continuous data were given as mean ± standard deviation(SD). The group differences were assessed by one-way ANOVA. Chi-square test was used to assess the frequency distribution in patients and controls. Odds ratios(ORs) and 95% confidence intervals(CIs) were calculated. A P-value < 0.05 was considered statistically significant, the Benjamini-Hochberg(BH) method was used to correct the P-values for multiple comparisons.Results: The average age was 28.855 ± 8.920 in patients [255(64.5%) males and 140(35.5%) females] and 27.924 ± 7.862 in controls [255(64.6%) males and 140(35.4%) females] and there was no statistical difference between patients and controls concerning age(t = 1.560, P = 0.119) and gender(χ2 = 0.001, P = 0.987). 384(96.0%) patients were HLA-B27 positive in AS group, and the BASFI and BASDAI score were 2.872 ± 2.067 and 4.009 ± 1.945, respectively. The quality results were very well, and all of the SNPs were in HWE in controls, except for rs16924144(χ2 = 4.166, P = 0.041). There were statistically significant differences in the genotype at rs1891385, rs10118795, rs10975519 and rs1048274(χ2 = 6.233, P = 0.044; χ2 = 7.397, P = 0.025; χ2 = 6.943, P = 0.031; χ2 = 6.532, P = 0.038). The allele frequencies did show a statistically at rs1891385, rs2210463, rs10118795, rs1929992(OR = 0.762, P = 0.014; OR = 1.265, P = 0.021; OR = 1.305, P = 0.009; OR = 1.248, P = 0.028). In recessive model, rs2210463, rs10118795, rs10975519 and rs1048274 were detected association with AS susceptibility(OR = 0.648, P = 0.027; OR = 0.627, P = 0.017; OR = 1.523, P = 0.009; OR = 1.509, P = 0.011), in dominant model the sites were rs1891385, rs16924144, rs10118795, rs1929992(OR = 0.706, P = 0.014; OR = 0.596, P = 0.001; OR = 1.346, P = 0.048; OR = 1.410, P = 0.027) and in homozygote were rs2210463, rs10118795, rs1929992(OR = 1.696, P = 0.015; OR = 1.803, P = 0.007; OR = 1.539, P = 0.036). Four SNPs(rs10118795, rs1929992, rs10975519, rs1048274) with high LD(D’ > 0.9, r2 > 0.7) after LD analysis. The SHEs platform found the haplotype TTCG was associated with a decreased risk for AS(OR = 0.766, P = 0.009). After adjustment using BH method, only the rs16924144, rs10118795, rs10975519 sites in recessive model, rs16924144 site in dominant model and haplotype TTCG were still associated with AS susceptibility. There were not association between the eight SNPs and the susceptibility and severity of AS.Conclusion: Our study suggests that the SNPs and the TTCG haplotype of the IL-33 gene may be associated with risk of AS. |
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