The *1244 A>G polymorphism of MyD88 (rs7744) is closely associated with susceptibility to ulcerative colitis

Abstract

Abstract. Toll-like receptor activation intitially recruits the myeloid differentiation primary response gene (88) (MyD88) protein. A polymorphism *1244 A>G (rs7744) in the 3'-untranslated region of MyD88 has been identified. In the present study, the association of this polymorphism with ulcerative colitis (UC) was investigated. The population studied comprised 922 individuals, including patients with UC (UC cases) and without (controls). Genotyping of rs7744 was performed by PCR single-strand conformation polymorphism and the rs7744 G allele frequencies in the controls and UC cases were 32.8 and 43.5%, respectively (P<0.0001). The results showed that the genotype frequency of the AA homozygote was significantly lower and that of the GG homozygote was significantly higher in the UC cases compared with those in the controls (P=0.0012 for both groups). The rs7744 minor allele variants were significantly associated with susceptibility to UC as indicated by dominant and recessive genetic models. The minor allele variants were associated with an increased risk for UC in the male individuals but not the female individuals. The rs7744 was also associated with a non-continuous phenotype of UC and steroid unused/independent UC. This minor allele homozygote was associated with the disease severity of UC, hospitalization and response to steroid treatment. The results of the present study provided evidence that MyD88 polymorphism rs7744 was significantly associated with the development of UC and that this polymorphism may be associated with the response to treatment therapies for

Two Genetic Variations in the IRF8 region are associated with Behçet’s disease in Han Chinese

“…MYD88 protein is a vital signal transducing adaptor protein in the TLR pathway due to its interaction with the interleukin-1 receptor-associated kinase 50 . One SNP of MYD88, namely rs7744 was reported to be associated with ulcerative colitis 25 . Nevertheless, no significant associations of rs7744 with BD and VKH were revealed in our study.…”

“…Myeloid differentiation factor 88 (MYD88) is another protein that participates in the TRIM-mediated TLR pathway 19 . Lately, gene polymorphisms of the participants in the TRIM-mediated TLR pathway, such as TRIM20, TRIM21, IRF3, IRF7, IRF8, NF-κB1-encoding P50 protein and MYD88 have been identified as risk factors that can predispose to a variety of autoimmune and autoinflammatory disorders 20 21 22 23 24 25 26 . Their possible role in uveitis has not yet been studied and was therefore the subject of the study presented here.…”

Evidence of activation of the Toll-like receptor-4 proinflammatory pathway in patients with schizophrenia

“…There are only a few studies of the presence or functional role of this polymorphism in human disorders. MyD88 rs7744 has been associated with autoimmune or inflammatory processes, [52][53][54] but its biological function has not yet been identified. As it is located in the 3' untranslated region (UTR) region, MyD88 rs7744 could influence the stability of mRNA, thereby compromising normal protein levels.…”

TNFAIP3, TNIP1, and MyD88 Polymorphisms Predict Septic-Shock-Related Death in Patients Who Underwent Major Surgery

“…On the other hand, MyD88 is an adapter protein used by almost all TLRs to activate NF-κB. The rs7744 SNP, located at the untranslated region of MyD88 , has been previously associated with the development of chronic inflammatory diseases, such as ulcerative colitis [51], Buerger disease [52], and coronary artery disease [53]. The function of the rs7744 SNP has not been identified yet, but it has been suggested that it could affect the binding of several microRNAs (miRNAs) [52].…”