Replication of Identified Inflammatory Bowel Diseases Genetic Associations: A Case–Control Study in the Tunisian Population

Abstract

Inflammatory bowel diseases (IBD) -Crohn's disease (CD) and ulcerative colitis (UC) -are chronic gastrointestinal inflammatory disorders with a complex genetic background. A genome wide association scan by the Welcome Trust Case Control Consortium (WTCCC) recently identified several novel susceptibility loci. We performed a replication study in 107 IBD patients (39 CD and 68 UC) and 162 controls. In total, 19 single nucleotide polymorphisms (SNPs) from previously identified susceptibility genes PTPN11, TNF α, IL23R, PTPN2, PTPN22, IL2 and IL10 were studied. In UC, we confirmed the association with PTPN2 (rs254215, GG, P=0.013, P corr =0.039; OR= 6.23 (1.18; 32.95)). In CD, we confirmed a marginal association with ((rs11066320, GG, P=0.018, P corr =0.054, OR= 0.4 (0.19; 0.82)). No significant association was found at the allele and genotype levels of SNPs in TNF α, IL23R, PTPN22, IL2, and IL10. However, on the haplotype analysis the AG haplotype of TNFα was more frequent in CD patients compared to controls (23.1% vs. 13.7%; P = 0.039; OR= 1.89 (1.02; 3.5)). The PTPN11 ATG haplotype was also more frequent in CD patients compared to controls (32.1% vs 21.3%; P = 0.04; OR= 1.75 (1.01; 3.01). These results reveal limited replication in Tunisian population and indicate differences in genetic architecture between populations.