The aim of this study was to perform a meta-analysis to derive precise estimation of the association of interleukin-23 receptor (IL-23R), IL-1 receptor 2 (IL-1R2), IL-12 beta (IL-12B), IL-10 and tumour necrosis factor (TNF)-α polymorphisms with ankylosing spondylitis (AS) susceptibility.
The aim of this study was to investigate the diagnostic and prognostic role of 5 single-nucleotide polymorphisms related to IL-23 pathway and IL-1 cluster genes in AS patients.
This study shows that a functional variant of miR-196a2 confers risk for BD but not for VKH syndrome or AAU(+)AS(+) by modulating the miR-196a gene expression and by regulating pro-inflammatory IL-1β and MCP-1 production.
In addition to the three known IL-1 polymorphisms, rs2856836, rs17561, and rs1894399, found in previous meta-analysis, this meta-analysis shows that the IL-1F10.3 and IL-1A+889 polymorphisms are associated with the development of AS in Europeans but not in Asians.
The allele and genotype frequencies of the polymorphisms were determined: The IL1α rs1800587, IL1βrs16944 and IL1βrs1143634 were not significantly associated with AS.
This study reports four genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.
A retrospective meta-analysis of three previous whole genome linkage scans confirmed a strong linkage at chromosome 16q and moderate linkage at sites on chromosomes 3, 10, and 19q, and a meta-analysis of studies of the interleukin-1 (IL-1) region genes in ankylosing spondylitis suggested the susceptibility to be conferred by the IL-1A gene.
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).
Regions previously associated with AS on chromosome 2q (the IL-1 gene cluster) and 22q (CYP2D6) exhibited nominal linkage in the meta-analysis, providing further statistical support for their involvement in susceptibility to AS.
However, several independent groups have reported significant associations between ankylosing spondylitis and the IL-1 gene cluster on the long arm of chromosome 2.
In the current study, we describe strong association and transmission of IL-1 family gene cluster single-nucleotide polymorphisms and haplotypes with AS.
As the marker D2S160 has been characterized as a candidate locus for Ankylosing Spondylitis (AS) after a genome-wide scan, and since this locus is located approximately 0.3 cM telomeric to the IL-1 gene cluster, we hypothesized that these cytokines might be good candidates for Spondylarthropathies (SpA).
This report of an association with a polymorphic site within the IL-1 locus and AS suggests that genes other than B27 may well be involved in the pathogenesis of AS.