Relationship Between IL1 Gene Polymorphism and Susceptibility to Ankylosing Spondylitis: An Updated and Supplemented Meta-Analysis

Abstract

The literature has provided inconsistent findings on the relationship between interleukin IL-1 gene polymorphisms and susceptibility to ankylosing spondylitis (AS). Therefore, a systematic review and meta-analysis were conducted. Online electronic database searches were performed for relevant research published as of May 2021. Meta-analysis was performed to compare alleles and multiple genetic models (including dominant, recessive, heterozygous, and homozygous models) using random-effects models to reduce the impact of heterogeneity. A 95% confidence interval (95% CI) odds ratio (OR) was used to assess potential relationships. Nineteen studies including 6235 patients with AS and 5919 healthy controls were recruited. IL-1A-889 (rs1800587) had statistical significance in the allelic model (OR 1.38, 95% CI 1.08-1.77, P = 0.010) (I² = 51%.1, P = 0.0001); homozygous model (OR 1.92, 95% CI 1.27-2.89, P = 0.002); heterozygous model (OR 1.49, 95% CI 1.02-2.17, P = 0.163); dominant genetic model (OR 1.53, 95% CI 1.05-2.24, P = 0.026); and recessive model (OR 1.54, 95% CI 1.04-2.28, P = 0.031). Further stratified analysis showed that the allele model (OR 1.35, 95% CI 1.08-1.69, P = 0.008), heterozygous model (OR 1.45, 95% CI 1.07-1.96, P = 0.017), and dominant model (OR 1.49, 95% CI 1.11-1.99, P = 0.007) in the English population and allele model (OR 2.21, 95% CI 1.45-3.37, P = 0.0001), homozygous model (OR 3.85, 95% CI 1.38-10.76, P = 0.010), heterozygous model (OR 3.42, 95% CI 1.85-6.32, P = 0.0001), and dominant model (OR 3.49, 95% CI 1.93-6.30, P = 0.001) in Tunis were significantly associated with susceptibility to AS. Analysis of the IL1F7 exon 2 (rs3811047) showed that the G allele frequency was higher in the normal population than in the AS population (OR 0.76, 95% CI (0.64, 0.91)). Further stratified analysis concluded that the allele model was significantly associated with AS susceptibility in Canadian (OR 0.76, 95% CI 0.61-0.94, P = 0.011) and Chinese patients (OR 0.64, 95% CI 0.41-0.98, P = 0.041). The meta-analysis showed that the IL-1 gene polymorphism IL-1A-889 (rs1800587) increases the risk of AS in English and Tunisian populations. IL1F7 exon 2 (rs3811047) is negatively correlated with susceptibility to AS in Canadian and Chinese populations, but additional studies are needed for further exploration.

Keywords: Ankylosing spondylitis; Interleukin-1; Meta-analysis; Polymorphism.