Genetic Polymorphisms Of Cd14, Toll-Like Receptor-2 And Manan-Binding Lectin In Ulcerative Colitis

Ulcerative colitis (UC) is a multi-factorial disease resulting from a complex interaction of genetic and environmental factors. Strong evidence suggests that the biology of the innate immunity receptors is of central importance in the host response to the environment. Therefore, one of our recent projects has been designed mainly on the identification of genetic alterations in Japanese patients with UC, with an attempt to clarify the association between molecular variations that alter the innate immune response and the pathogenesis of UC. The aim of the present study was to investigate the association between polymorphisms of Toll-like receptor (TLR)2, CD14, and Manning binding lectin (MBL) genes to the pathogenesis of UC in Japanese patients. A total of 105 UC patients and 147 healthy control subjects were enrolled in this study. Polymorphisms in the promoter of CD14 gene at C-260T and point mutations at codon 54 of exon 1 of the MBL gene were investigated by polymerase chain reaction based restriction fragment length polymorphism, while -196 to-174 del in the promoter of TLR2 was investigated by allele specific polymerase chain reaction method. The frequencies of CD14TT and T carrier were significantly higher in UC patients than those in the controls. (OR4.07; 95%CI, 1.87-8.90, P=0.0003; OR3.05; 95%CI, 1.50-6.19, P=0.001, respectively.). Of all UC patients, TT and T carriers of CD14 were more closely associated with the risk of distal colitis phenotype. (Distal colitistype: OR=7.78; 95%CI, 2.14-28.28, p=0.0007; Total colitis: OR=6.30; 95%CI, 2.71-14.58, p=0.005, respectively.). Although the frequency of TLR2-196 to-174 del carrier was higher in UC patients than that in the controls, the difference was not of significance (55.6□% v.s. 49.3%, P=0.36). However, the carrier frequency of TLR2 in steroid-dependant cases (75%, 18/24) was significantly higher than that in the control subjects (OR=3.09; 95%CI, 1.16-8.926, P=0.026). In addition, no significant difference in point mutations at codon 54 of exon 1 of MBL was found between UC patients and health control subjects(43□% v.s. 33.3%, P=0.125). These results suggest that existence of a genetic polymorphism in promoter of CD14 may be associated with an increased susceptibility to developing UC, especially for distal type colitis. Furthermore, TLR2 polymorphism may be of potential importance to an increased risk of developing steroid-dependant UC cases. Although a few studies reported an association between MBL polymorphism and the clinical development of sporadic UC, our data indicate that MBL polymorphism may play a relatively unimportant role in the pathogenesis of UC in Japanese population.