Dataset Information

Toll-like receptor 9 gene mutations and polymorphisms in Japanese ulcerative colitis patients.

ABSTRACT: AIM:To investigated gene mutations and polymorphisms of TLR9 in Japanese ulcerative colitis (UC) patients. METHODS:Three single nucleotide polymorphisms (SNPs) in TLR9 were identified in healthy controls, and were assessed in 48 UC patients and 47 healthy controls. Control subjects were matched for age, sex and date of blood sampling from among a subgroup of participants. RESULTS:TLR9 -1486CC, 1174GG and 2848AA increase the risk of UC [odds ratio (OR) 2.64, 95% confidence interval (95% CI): 1.73-6.53, P = 0.042], and TLR9 -1486TT, 1174AA and 2848GG decrease the risk of UC (OR 0.30, 95% CI: 0.10-0.94, P = 0.039), although there were no correlations between SNPs and disease phenotype or TLR9 mRNA expression. CONCLUSION:TLR9 polymorphisms are associated with increased susceptibility to UC.

SUBMITTER: Fuse K

PROVIDER: S-EPMC3001972 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Toll-like receptor 9 gene mutations and polymorphisms in Japanese ulcerative colitis patients.

Fuse Kaori K Katakura Kyoko K Sakamoto Natsumi N Ohira Hiromasa H

World journal of gastroenterology 20101201 46

<h4>Aim</h4>To investigated gene mutations and polymorphisms of TLR9 in Japanese ulcerative colitis (UC) patients.<h4>Methods</h4>Three single nucleotide polymorphisms (SNPs) in TLR9 were identified in healthy controls, and were assessed in 48 UC patients and 47 healthy controls. Control subjects were matched for age, sex and date of blood sampling from among a subgroup of participants.<h4>Results</h4>TLR9 -1486CC, 1174GG and 2848AA increase the risk of UC [odds ratio (OR) 2.64, 95% confidence i ...[more]

PMID: 21155002

Similar Datasets

Project description:Glucocorticoids (GCS) remain one of the mainstay treatments in the management of ulcerative colitis (UC) but up to a third of patients will ultimately fail to respond and progress to a more severe and difficult to manage disease state. Previous clinical studies suggest that the Toll-Like Receptor 9 (TLR9) agonist DIMS0150 not only induces production of key anti-inflammatory cytokines as IL-10 but interestingly also enhances steroid sensitivity in steroid refractory UC patients. We investigated, in the context of a clinical study, whether a pre-selection of steroid response genes could identify steroid refractory UC subjects most likely to respond to DIMS0150 treatment.In a non-interventional pilot study, blood from steroid refractory UC patients and healthy volunteers was taken and thirty-four previously described steroid response genes were analysed by real time PCR analysis. To establish clinical utility of the identified biomarkers, a placebo controlled, randomized, double blinded study in active steroid dependent and steroid resistant UC patients on concomitant steroid therapies was used (EudraCT number: 2006-001846-15).We identified three potential biomarkers CD163, TSP-1 and IL-1RII whose response to steroids was significantly enhanced when DIMS0150 was applied. Thirty-four subjects were randomized to receive a single rectal administration of placebo or 30 mg of DIMS0150. Blood derived PBMCs were obtained prior to dosing and assayed for evidence of a steroid enhancing effect following steroid incubation in the presence of DIMS0150. Comparison to established steroid sensitivity marker IL-6 confirmed that clinical responders are steroid refractory UC patients. Upon study completion and un-blinding, the biomarker assay correctly predicted a clinical response in over 90% of the patients.Using specific steroid response biomarkers, GCS refractory UC patients most likely to benefit from DIMS0150 treatment could be identified and illustrates the usefulness of a personalized treatment approach.

Dataset Information

Toll-like receptor 9 gene mutations and polymorphisms in Japanese ulcerative colitis patients.

Publications

Toll-like receptor 9 gene mutations and polymorphisms in Japanese ulcerative colitis patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets