Volume 141, Issue 2, Pages (August 2011)

Slides:



Advertisements
Similar presentations
Volume 133, Issue 2, Pages (August 2007)
Advertisements

Christian F. Krieglstein, Christoph Anthoni, Wolfgang H
Volume 131, Issue 4, Pages (October 2006)
Volume 128, Issue 2, Pages (February 2005)
Identification of EpCAM as the Gene for Congenital Tufting Enteropathy
Volume 387, Issue 10014, Pages (January 2016)
Ashwin N. Ananthakrishnan, Millie D. Long, Christopher F
Volume 144, Issue 5, Pages e10 (May 2013)
Volume 140, Issue 2, Pages e2 (February 2011)
Volume 153, Issue 2, Pages (August 2017)
Volume 137, Issue 2, Pages e2 (August 2009)
Volume 135, Issue 4, Pages (October 2008)
Volume 136, Issue 2, Pages (February 2009)
Volume 132, Issue 4, Pages (April 2007)
Volume 138, Issue 4, Pages (April 2010)
Volume 143, Issue 5, Pages e4 (November 2012)
Volume 141, Issue 2, Pages e4 (August 2011)
Volume 133, Issue 2, Pages (August 2007)
Type I IL-1 Receptor Mediates IL-1 and Intracellular IL-1 Receptor Antagonist Effects in Skin Inflammation  Gaby Palmer, Dominique Talabot-Ayer, Gürkan.
Ira J. Fox, Stephen C. Strom  Gastroenterology 
Volume 10, Issue 1, Pages (January 2015)
Volume 127, Issue 2, Pages (August 2004)
Volume 128, Issue 2, Pages (February 2005)
Making Sense of HDAC2 Mutations in Colon Cancer
Volume 144, Issue 5, Pages e6 (May 2013)
Volume 142, Issue 2, Pages e2 (February 2012)
Volume 139, Issue 4, Pages e3 (October 2010)
Eva Wertheimer, Marcelo G. Kazanietz  Gastroenterology 
Volume 153, Issue 3, Pages e16-e17 (September 2017)
Volume 133, Issue 6, Pages (December 2007)
Steven R. Brant  Clinical Gastroenterology and Hepatology 
Volume 147, Issue 3, Pages e2 (September 2014)
Volume 135, Issue 2, Pages (August 2008)
Volume 17, Issue 14, Pages (July 2007)
Volume 134, Issue 4, Pages e2 (April 2008)
Volume 147, Issue 1, Pages (July 2014)
Volume 139, Issue 6, Pages (December 2010)
Volume 139, Issue 6, Pages (December 2010)
Volume 144, Issue 2, Pages (February 2013)
The Genetics of Inflammatory Bowel Disease
Weight Loss after Gastric Bypass Is Associated with a Variant at 15q26
Volume 132, Issue 5, Pages (May 2007)
Volume 142, Issue 4, Pages e2 (April 2012)
Volume 145, Issue 2, Pages (August 2013)
Volume 138, Issue 4, Pages (April 2010)
Volume 138, Issue 4, Pages (April 2010)
This Month in Gastroenterology
Suppression of Apoptosis, Crypt Hyperplasia, and Altered Differentiation in the Colonic Epithelia of Bak-Null Mice  Carrie A. Duckworth, D. Mark Pritchard 
Volume 134, Issue 7, Pages e3 (June 2008)
Assessment of the Genetic Basis of Rosacea by Genome-Wide Association Study  Anne Lynn S. Chang, Inbar Raber, Jin Xu, Rui Li, Robert Spitale, Julia Chen,
Covering the Cover Gastroenterology
Genome-Wide Association Studies: Present Status and Future Directions
Genetic Investigations of Kidney Disease: Core Curriculum 2013
Volume 153, Issue 2, Pages (August 2017)
Expression Quantitative Trait Loci Analysis Identifies Associations Between Genotype and Gene Expression in Human Intestine  Boyko Kabakchiev, Mark S.
The PepT1–NOD2 Signaling Pathway Aggravates Induced Colitis in Mice
A2B Adenosine Receptor Gene Deletion Attenuates Murine Colitis
Antigen-Presenting Cell Production of IL-10 Inhibits T-Helper 1 and 17 Cell Responses and Suppresses Colitis in Mice  Bo Liu, Susan L. Tonkonogy, R. Balfour.
Volume 135, Issue 2, Pages e2 (August 2008)
Time Trends of Ulcer Mortality in Europe
Identification of a genetic variant associated with abdominal aortic aneurysms on chromosome 3p12.3 by genome wide association  James R. Elmore, MD, Melissa.
Ling Zheng, Terrence E. Riehl, William F. Stenson  Gastroenterology 
Volume 139, Issue 4, Pages (October 2010)
Volume 141, Issue 3, Pages (September 2011)
Volume 132, Issue 2, Pages (February 2007)
Volume 139, Issue 2, Pages (August 2010)
Javier Oliver, Blanca Rueda, Miguel A
Volume 155, Issue 6, Pages (December 2018)
Volume 136, Issue 7, Pages (June 2009)
Genetic Polymorphisms in the Polycomb Group Gene EZH2 and the Risk of Lung Cancer  Kyong-Ah Yoon, MD, Hye Jin Gil, MS, Jihye Han, MS, Jaehee Park, MS,
Presentation transcript:

Volume 141, Issue 2, Pages 633-641 (August 2011) Single Nucleotide Polymorphisms That Increase Expression of the Guanosine Triphosphatase RAC1 Are Associated With Ulcerative Colitis  Aleixo M. Muise, Thomas Walters, Wei Xu, Grace Shen–Tu, Cong–Hui Guo, Ramzi Fattouh, Grace Y. Lam, Victorien M. Wolters, Joshua Bennitz, Johan van Limbergen, Paul Renbaum, Yair Kasirer, Bo–Yee Ngan, Dan Turner, Lee A. Denson, Philip M. Sherman, Richard H. Duerr, Judy Cho, Charlie W. Lees, Jack Satsangi, David C. Wilson, Andrew D. Paterson, Anne M. Griffiths, Michael Glogauer, Mark S. Silverberg, John H. Brumell  Gastroenterology  Volume 141, Issue 2, Pages 633-641 (August 2011) DOI: 10.1053/j.gastro.2011.04.057 Copyright © 2011 AGA Institute Terms and Conditions

Figure 1 RAC1 imputation analysis. Regional blots plot of the negative decadic logarithm of the P values of SNPs in the RAC1 region, including both (diamonds) genotyped and (asterisks) imputation SNPs, based on the 2049 individuals from the discovery cohort. In IBD, the strongest signal comes from 3 SNPs (rs836472, rs1880118, and rs12536544) located at 6401429–6402426 of chromosome 7 that are in strong LD (r2 >0.80) with rs10951982. RAC1 gene is depicted below LD plot with genotyped SNP in bold and r2 SNP map. Gastroenterology 2011 141, 633-641DOI: (10.1053/j.gastro.2011.04.057) Copyright © 2011 AGA Institute Terms and Conditions

Figure 2 RAC1 expression based on genotype. (A) Plot of logarithm (base 10) of odds score (y-axis) and SNP position of each chromosome (x-axis). The expression quantitative trait loci maximal LOD score on chromosome 7 is the RAC1 SNP (rs12536544) that is in strong disequilibrium to rs10951982 (r2 of 0.82 to 1.0). (B) RAC1 expression from messenger RNA isolated from peripheral blood cells from 16 IBD patients with colonic disease based on rs10951982 genotype. “G” allele is the risk allele. Expression was normalized to β-actin expression. Wilcoxon exact test. Gastroenterology 2011 141, 633-641DOI: (10.1053/j.gastro.2011.04.057) Copyright © 2011 AGA Institute Terms and Conditions

Figure 3 Impact of impairing Rac1 function in DSS-induced colitis in mice. (A) Rac1-KO. Left panel graphs show changes in weight with DSS treatment. Middle panel shows changes in rectal bleeding. # at risk indicates number of mice not bleeding at each time point. Right panel shows Disease Activity Index. Error bars represent standard error of mean. (B) Colonic MPO activity. Colonic neutrophil infiltration was measured by MPO activity. MPO activity was assessed in the distal colon of WT mice (WT + water), Rac1-KO mice (Rac1-KO + water), and Rac1-KO mice treated with 5% DSS (Rac1-KO + DSS). (Wilcoxon rank sum test; error bars represent standard error of mean). (C) Colonic cytokine assay. Cytokine assays performed using Meso Scale Discovery mouse TH1/TH2 9-plex assay kit (Gaithersburg, MD). (Mann–Whitney test, 2-tailed; error bars represent standard error of mean). Gastroenterology 2011 141, 633-641DOI: (10.1053/j.gastro.2011.04.057) Copyright © 2011 AGA Institute Terms and Conditions