Ulcerative Colitis is Associated with a Promoter Polymorphism of Lipopolysaccharide Receptor Gene, CD14

Obana, Nobuya; Takahashi, Shizuko; Kinouchi, Yoshitaka; Negoro, Kenichi; Takagi, Sho; Hiwatashi, Nobuo; Shimosegawa, Tooru

doi:10.1080/00365520212504

Cited by 69 publications

(14 citation statements)

References 40 publications

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“…Compared with the previous studies, the frequency of the CC genotype of healthy controls in Korean population (41.6%) was higher than in Chinese (15.6%) or Japanese (21.8%), whereas the TT genotype of healthy controls in Korean (14.6%) was lower than in Chinese (36.3%) or Japanese (25.4%) (12, 13). Further study in larger and diverse populations would be needed for elucidation of the association between disease susceptibility of IBD and polymorphism of CD14 gene.…”

Section: Discussioncontrasting

confidence: 71%

“…Previously, in several reports from Western countries, gene polymorphisms of the CD14 was found to be associated with the development of IBD, more so in the development of CD than in UC (9, 10). However, in Japanese population, the same genotype is associated with UC but not with CD (12, 15), and another study investigating Chinese patients failed to demonstrate any association (13). In our results, T allele and TT genotype frequencies of CD14 gene were significantly higher in IBD patients than in healthy controls.…”

Section: Discussionmentioning

confidence: 95%

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Association Between Toll-Like Receptors/CD14 Gene Polymorphisms and Inflammatory Bowel Disease in Korean Population

et al. 2012

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The innate immune response in patients who develop inflammatory bowel disease (IBD) may be abnormal. However, the exact role of Toll-like receptors (TLRs) / CD14 gene in the pathogenesis of IBD has not been fully elucidated. We aimed to investigate the association between polymorphisms of TLR1, 2, 4, 6, and CD14 gene and susceptibility to IBD in Korean population. A total 144 patients of IBD (99 patients with ulcerative colitis, 45 patients with Crohn's disease) and 178 healthy controls were enrolled. Using a PCR-RFLP, we evaluated mutations of TLR1 (Arg80Thr), TLR2 (Arg753Gln and Arg677Trp), TLR4 (Asp299Gly and Thr399Ile), TLR6 (Ser249Pro) genes and the -159 C/T promoter polymorphism of CD14 gene. No TLR polymorphisms were detected in Korean subjects. T allele and TT genotype frequencies of CD14 gene were significantly higher in IBD patients than in healthy controls. In subgroup analysis, T allelic frequency was higher in pancolitis phenotype of ulcerative colitis. In Korean population, the promoter polymorphism at -159 C/T of the CD14 gene is positively associated with IBD, both ulcerative colitis and Crohn's disease.

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Section: Discussioncontrasting

confidence: 71%

Section: Discussionmentioning

confidence: 95%

Association Between Toll-Like Receptors/CD14 Gene Polymorphisms and Inflammatory Bowel Disease in Korean Population

et al. 2012

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“…The relevance of a variant on the CD14 gene at position c.1-260C>T has been investigated for CD and UC by three other groups [34,35,36,37]. One of these studies [36] looked at a Japanese cohort of 101 UC patients, 82 CD patients and 123 healthy controls.…”

Section: Discussionmentioning

confidence: 99%

“…One of these studies [36] looked at a Japanese cohort of 101 UC patients, 82 CD patients and 123 healthy controls. The authors reported T allele frequencies of 57.4% for UC, 48.2% for CD and 44.7% for healthy controls as well as TT homozygote genotype frequencies of 37.6% for UC, 25.5% for CD and 23.6% for healthy controls.…”

Section: Discussionmentioning

confidence: 99%

The c.1-260C>T Promoter Variant of CD14 but Not the c.896A>G (p.D299G) Variant of Toll-Like Receptor 4 (TLR4) Genes Is Associated with Inflammatory Bowel Disease

et al. 2007

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Background: Inflammatory bowel disease (IBD) results from an aberrant immune response to the indigenous intestinal flora in genetically susceptible hosts. Therefore, the study of candidate genes involved in host pathogen interactions is of key interest. Methods: In this two-center, retrospective German and Hungarian cohort study, patients with Crohn’s disease (CD) (n = 379; German n = 235, Hungarian n = 144) and ulcerative colitis (UC) (n = 263; German n = 145, Hungarian n = 118) and healthy controls (n = 605; German n = 403, Hungarian n = 202) were genotyped for the presence of the CD14 c.1-260C>T promoter variant and the TLR4 c.896A>G (p.D299G) variant by melting curve analysis using fluorescence resonance energy transfer probes. Data were stratified according to the presence of NOD2 (CARD15) mutations and a detailed genotype-phenotype analysis was performed. Results: In the German cohort the CD14 single-nucleotide polymorphism was associated with UC, but not CD (UC p = 0.016 vs. CD p = 0.190), while the opposite was found in the Hungarian cohort (UC p = 0.083 vs. CD p = 0.019). No association of IBD with the TLR4 single-nucleotide polymorphism was found in either cohort (UC p = 0.430, CD p = 0.783 vs. UC p = 0.745, CD p = 0.383). Conclusion: IBD appears to be associated with the CD14 c.1-260C>T promoter variant in Germans and Hungarians, but not with the TLR4 c.896A>G (p.D299G) variant.

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“…On the other hand, Ly6C hi monocytes differentiate into dominant pro-inflammatory effector cells in the inflamed gut due to the up-regulation of TLR2 and NOD2 (Zigmond, et al, 2012). Furthermore, CD14-expressing macrophages that are more sensitive to LPS (Lee, et al, 1992) are increased in the intestinal mucosa of IBD patients compared to healthy controls (Obana, et al, 2002) and might contribute to the initiation and maintenance of the inflammatory environment. Thus, not only the regulation of the respective target molecules itself, but also the modulation of receptors and signaling pathways influenced by their expression might represent promising targets for clinical intervention.…”

Section: Discussionmentioning

confidence: 99%

Perturbations of mucosal homeostasis through interactions of intestinal microbes with myeloid cells

2015

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Mucosal surfaces represent the largest areas of interactions of the host with its environment. Subsequently, the mucosal immune system has evolved complex strategies to maintain the integrity of the host by inducing protective immune responses against pathogenic and tolerance against dietary and commensal microbial antigens within the broad range of molecules the intestinal epithelium is exposed to. Among many other specialized cell subsets, myeloid cell populations - due to their strategic location in the subepithelial lamina propria - are the first ones to scavenge and process these intestinal antigens and to send consecutive signals to other immune and non-immune cell subsets. Thus, myeloid cell populations represent attractive targets for clinical intervention in chronic inflammatory bowel diseases (IBDs) such as ulcerative colitis (UC) and Crohn's disease (CD) as they initiate and modulate inflammatory or regulatory immune response and shape the intestinal T cell pool. Here, we discuss the interactions of the intestinal microbiota with dendritic cell and macrophage populations and review in this context the literature on four promising candidate molecules that are critical for the induction and maintenance of intestinal homeostasis on the one hand, but also for the initiation and propagation of chronic intestinal inflammation on the other.

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Ulcerative Colitis is Associated with a Promoter Polymorphism of Lipopolysaccharide Receptor Gene, CD14

Cited by 69 publications

References 40 publications

Association Between Toll-Like Receptors/CD14 Gene Polymorphisms and Inflammatory Bowel Disease in Korean Population

Association Between Toll-Like Receptors/CD14 Gene Polymorphisms and Inflammatory Bowel Disease in Korean Population

The c.1-260C>T Promoter Variant of CD14 but Not the c.896A>G (p.D299G) Variant of Toll-Like Receptor 4 (TLR4) Genes Is Associated with Inflammatory Bowel Disease

Perturbations of mucosal homeostasis through interactions of intestinal microbes with myeloid cells

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