Genetic association and phenotypic correlation of TLR4 but not NOD2 variants with Tunisian inflammatory bowel disease

OBJECTIVE The common association of NOD2/CARD15 and TLR4 genes variants with inflammatory bowel disease (IBD) have not been universally replicated. We aimed to study the polymorphism of these two genes in Tunisian patients with IBD. METHODS Polymorphism of NOD2 (R702W, G908R and 1007fs) and TLR4 (Asp299Gly and Thr399Ile) genes were analyzed in 106 IBD patients (68 ulcerative colitis (UC), 38 Crohn's disease (CD)) and 160 healthy controls using PCR-RFLP. A genotype-phenotype correlation was performed. RESULTS The mutated allele of TLR4-Thr399Ile was strongly associated to the disease (9.4% in IBD, 7.4% in UC, 13.2% in CD Versus 2.5% in controls; p values 4.10-4; 0.014; 6.10-5 respectively). Frequencies of the heterozygous genotypes were significantly higher in IBD (17%), UC (14.7%) and CD patients (21.1%) in comparison with controls (5%) (p 0.0012; 0.012 and 0.001 respectively). Interestingly, the CC wild genotype was found to be protective (OR 0.24). The mutated allele of TLR4-Asp299Gly was more frequent in controls (6.8%) than in IBD patients (2.9%). A phenotypic correlation of Asp299Gly-AG genotype with arthritis in UC patients was detected (p= 0.003). Regarding NOD2 gene, the studied SNPs were not polymorphic and there was no genetic association or phenotypic correlation with gene variants. CONCLUSION In our study, TLR4-Thr399Ile variant is strongly associated with the susceptibility to IBD whereas, TLR4-Asp299Gly seem to play a role in the clinical expression of UC. The rarity and non association of the NOD2 mutations with IBD in our study may reveal a genetic characteristic of the disease in our region.