Ankylosing spondylitis: analysis of gene-gene interactions between IL-12β, JAK2, and STAT3 in Han Chinese and Algerian cohorts

INTRODUCTION: Association studies have recently identified the importance of new genetic variants for ankylosing spondylitis (AS) in several populations. Our aim was to confirm associations of variants within genes involved in the IL-23 signalling pathway with AS in two ethnically different populations: Han Chinese and Algerian. MATERIAL AND METHODS: Two case-control studies were performed in separate cohorts: Han Chinese (430 AS patients and 580 controls) and Algerian (130 AS patients and 120 controls). We genotyped four single nucleotide polymorphisms (SNPs): rs3212227 (or +1188A/C) and rs6887695 in IL-12β, rs7857730 in JAK2, and rs2293152 in STAT3, using TaqMan SNP genotyping assays. Gene-gene interaction analyses were also tested by logistic regression and multifactor dimensionality reduction (MDR). RESULTS: Statistical analysis revealed a difference in allele frequencies between AS patients and controls for rs321222 in the IL-12β gene in both the Han Chinese (p = 0.005) and the Algerian (p = 0.031) cohorts. Two other associations were reported with JAK2 rs7857730 in the Han Chinese (allelic p = 0.014) cohort and STAT3 rs2293152 in the Algerian (allelic p = 0.006) cohort. Moreover, logistic regression analyses showed a number of significant combinations within the two populations, and the gene-gene epistasis effects in AS were also confirmed by MDR. CONCLUSIONS: Our findings have confirmed the association between genes in IL-23 signalling pathway and the pathogenesis of AS. This association was particularly novel in both Han Chinese and Algerian populations with the 3’ untranslated region (3’UTR) variant rs3212227 (or +1188A/C) of IL-12β. The gene-gene interaction models in this pathway may thus increase the risk of AS in these populations.