Search

Your search keyword '"Richard, N."' showing total 42 results
Start Over Author "Richard, N." Publication Year Range Last 10 years Journal gastroenterology (00165085) Publisher elsevier b.v.
42 results on '"Richard, N."'

2. X Chromosome Contribution to the Genetic Architecture of Primary Biliary Cholangitis.

Author

Asselta, Rosanna, Paraboschi, Elvezia M., Gerussi, Alessio, Cordell, Heather J., Mells, George F., Sandford, Richard N., Jones, David E., Nakamura, Minoru, Ueno, Kazuko, Hitomi, Yuki, Kawashima, Minae, Nishida, Nao, Tokunaga, Katsushi, Nagasaki, Masao, Tanaka, Atsushi, Tang, Ruqi, Li, Zhiqiang, Shi, Yongyong, Liu, Xiangdong, and Xiong, Ma

Abstract

Genome-wide association studies in primary biliary cholangitis (PBC) have failed to find X chromosome (chrX) variants associated with the disease. Here, we specifically explore the chrX contribution to PBC, a sexually dimorphic complex autoimmune disease. We performed a chrX-wide association study, including genotype data from 5 genome-wide association studies (from Italy, United Kingdom, Canada, China, and Japan; 5244 case patients and 11,875 control individuals). Single-marker association analyses found approximately 100 loci displaying P < 5 × 10–4, with the most significant being a signal within the OTUD5 gene (rs3027490; P = 4.80 × 10–6; odds ratio [OR], 1.39; 95% confidence interval [CI], 1.028–1.88; Japanese cohort). Although the transethnic meta-analysis evidenced only a suggestive signal (rs2239452, mapping within the PIM2 gene; OR, 1.17; 95% CI, 1.09–1.26; P = 9.93 × 10–8), the population-specific meta-analysis showed a genome-wide significant locus in East Asian individuals pointing to the same region (rs7059064, mapping within the GRIPAP1 gene; P = 6.2 × 10–9; OR, 1.33; 95% CI, 1.21–1.46). Indeed, rs7059064 tags a unique linkage disequilibrium block including 7 genes: TIMM17B , PQBP1 , PIM2 , SLC35A2 , OTUD5 , KCND1 , and GRIPAP1 , as well as a superenhancer (GH0XJ048933 within OTUD5) targeting all these genes. GH0XJ048933 is also predicted to target FOXP3 , the main T-regulatory cell lineage specification factor. Consistently, OTUD5 and FOXP3 RNA levels were up-regulated in PBC case patients (1.75- and 1.64-fold, respectively). This work represents the first comprehensive study, to our knowledge, of the chrX contribution to the genetics of an autoimmune liver disease and shows a novel PBC-related genome-wide significant locus. [Display omitted] [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

13. Sa1967 - Ustekinumab is Effective for Inducing Clinical, Endoscopic, and Radiographic Response and Remission in Refractory Moderate-to-Severe Crohn's Disease: A Multicentre Cohort Study.

Author

Ma, Christopher, Fedorak, Richard N., Kaplan, Gilaad, Dieleman, Levinus A., Devlin, Shane M., Stern, Nathan, Kroeker, Karen I., Seow, Cynthia H., Leung, Yvette, Novak, Kerri L., Halloran, Brendan P., Huang, Vivian, Wong, Karen, Ghosh, Subrata, and Panaccione, Remo

Published
2017
Full Text
View/download PDF

29. Larazotide Acetate for Persistent Symptoms of Celiac Disease Despite a Gluten-Free Diet: A Randomized Controlled Trial.

Author

Leffler, Daniel A., Kelly, Ciaran P., Green, Peter H.R., Fedorak, Richard N., DiMarino, Anthony, Perrow, Wendy, Rasmussen, Henrik, Wang, Chao, Bercik, Premysl, Bachir, Natalie M., and Murray, Joseph A.

Abstract

Background & Aims Celiac disease (CeD) is a prevalent autoimmune condition. Recurrent signs and symptoms are common despite treatment with a gluten-free diet (GFD), yet no approved or proven nondietary treatment is available. Methods In this multicenter, randomized, double-blind, placebo-controlled study, we assessed larazotide acetate 0.5, 1, or 2 mg 3 times daily to relieve ongoing symptoms in 342 adults with CeD who had been on a GFD for 12 months or longer and maintained their current GFD during the study. The study included a 4-week placebo run-in, 12 weeks of treatment, and a 4-week placebo run-out phase. The primary end point was the difference in average on-treatment Celiac Disease Gastrointestinal Symptom Rating Scale score. Results The primary end point was met with the 0.5-mg dose of larazotide acetate, with fewer symptoms compared with placebo by modified intention to treat (n = 340) (analysis of covariance, P = .022; mixed model for repeated measures, P = .005). The 0.5-mg dose showed an effect on exploratory end points including a 26% decrease in celiac disease patient-reported outcome symptomatic days ( P = .017), a 31% increase in improved symptom days ( P = .034), a 50% or more reduction from baseline of the weekly average abdominal pain score for 6 or more of 12 weeks of treatment ( P = .022), and a decrease in the nongastrointestinal symptoms of headache and tiredness ( P = .010). The 1- and 2-mg doses were no different than placebo for any end point. Safety was comparable with placebo. Conclusions Larazotide acetate 0.5 mg reduced signs and symptoms in CeD patients on a GFD better than a GFD alone. Although results were mixed, this study was a successful trial of a novel therapeutic agent targeting tight junction regulation in patients with CeD who are symptomatic despite a GFD. Clinicaltrials.gov : NCT01396213 . [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results