A new study on the role of Toll-like receptor 4 and the pathogenesis of inflammatory bowel disease (IBD) entitled “Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms: new data and a meta-analysis” was published in BMC Gastroenterology by Dr. Nezha Senhaji from the Laboratory of Genetic and Molecular Pathology (LGPM) at Hassan II University in Morocco.
Inflammatory bowel disease is an idiopathic and chronic multifactorial disease of the gastrointestinal tract. It has been shown that IBD pathogenesis is associated with commensal bacterial flora and genes associated to the host immune system, but the precise mechanism is not clear.
The research team evaluated if the TLR4 gene was associated with Crohn’s disease (CD) and ulcerative colitis (UC) within Moroccan patients, and evaluated its correlation with clinical manifestation of the disease. Single nucleotide polymorphisms in toll-like receptor 4 (TLR4) causes an unusual immune response to local intestinal flora that may induce the development of inflammatory bowel disease.
The study enrolled 117 Moroccan patients, 83 with Crohn’s disease and 34 with ulcerative colitis, and 112 healthy unrelated blood donors. The diagnosis of CD or UC was determined based on standard clinical, endoscopic, radiological and histological criteria. CD was classified according to the Montreal classification. The case report form was based on questions about disease phenotype and location, age at diagnosis, toxicological behavior and additional clinical characteristics. The TLR4 polymorphisms, including Asp299Gly and Thr399Ile, were genotyped using polymerase chain reaction-restriction fragment length polymorphism. Meta-analysis was done to evaluate the correlation between 299Gly and 399Ileu single nucleotide polymorphism and CD, UC and the general probability of developing IBD.
The research team found that the incidence of the usual substitutions in the TLR4 gene, Asp299Gly and Thr399Ile, were not significantly different between patients and controls within the Moroccan population of the study. Nevertheless, meta-analysis demonstrated significantly higher frequencies of both Asp299Gly and Thr399Ile single nucleotide polymorphism in IBD and CD and for 399Ileu in UC patients. Finally, the researchers concluded that TLR4 single nucleotide polymorphisms induce a significant increased probability of developing in general IBD. Most like, the single nucleotide polymorphism in the TLR4 gene is associated with ethnic differences. Moreover, other genetic and environmental factors may have, within this population, a role in the development of IBD. Finally, the authors highlight that due to the small sample size of their study, additional studies have to be performed to confirm the present data.