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Genetic association and phenotypic correlation of TLR4 but not NOD2 variants with Tunisian inflammatory bowel disease
Author(s) -
Feki Sawsan,
Bouzid Dorra,
Abida Olfa,
Chtourou Lassaad,
Elloumi Nesrine,
Toumi Amina,
Hachicha Hend,
Amouri Ali,
Tahri Nabil,
Masmoudi Hatem
Publication year - 2017
Publication title -
journal of digestive diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 51
eISSN - 1751-2980
pISSN - 1751-2972
DOI - 10.1111/1751-2980.12552
Subject(s) - nod2 , genotype , inflammatory bowel disease , allele , ulcerative colitis , odds ratio , medicine , crohn's disease , tlr4 , immunology , gastroenterology , disease , genetics , gene , biology , inflammation
OBJECTIVE The common association between NOD2/CARD15 and TLR4 gene variants with inflammatory bowel disease (IBD) has not been replicated in all studies. We studied the polymorphism of these two genes in Tunisian patients with IBD. METHODS Polymorphisms of NOD2 (R702W, G908R and L1007fs) and TLR4 (Asp299Gly and Thr399Ile) genes were analyzed in 106 patients with IBD (68 with ulcerative colitis [UC], 38 with Crohn's disease [CD]) and 160 healthy controls using polymerase chain reaction‐restriction fragment length polymorphism. Genotypes and phenotypes were correlated. RESULTS The mutated allele of TLR4‐Thr399Ile was strongly associated with IBD (9.4% in IBD, 7.4% in UC and 13.2% in CD vs 2.5% in controls; P = 0.0004, 0.014 and 0.00006, respectively). Heterozygous genotypes were significantly more frequent in patients with IBD (17.0%), UC (14.7%) and CD (21.1%) than in controls (5.0%) ( P = 0.0012, 0.012 and 0.001, respectively). Interestingly, the wild genotype was found to be protective (odds ratio 0.24). The mutated allele of TLR4‐Asp299Gly was more frequent in controls (6.8%) than in patients with IBD (2.9%). A phenotypic correlation of Asp299Gly‐AG genotype with arthritis in UC patients was detected ( P = 0.003). Regarding the NOD2 gene, the common variations studied were not polymorphic and there was no genetic association with IBD. CONCLUSION The TLR4‐Thr399Ile variant was strongly associated with susceptibility to IBD, whereas TLR4‐Asp299Gly seems to play a role in the clinical expression of UC. The rarity and non‐association of NOD2 mutations with IBD may reveal a genetic characteristic of the population in our region.