OBJECTIVES: NOD2 mutations and anti-Saccharomyces cerevisiae antibodies (ASCAs) are established risk factors of Crohn's disease (CD) in whites but have not been assessed in African-American (AA) adults with CD. METHODS: AAs with CD and controls were recruited by the Mid-Atlantic African-American IBD Study as part of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium. Genotyping for the three common CD NOD2 mutations (Leu1007fsinsC, G908R/2722g>c, and R702W/2104c>t) and ASCA enzyme-linked immunosorbent assays were performed in 183 AA CD patients and in 143 controls. Logistic regression was used to calculate adjusted odds ratios (ORs) for the association between ASCA and disease phenotype. RESULTS: ASCA sensitivity and specificity values were 70.5 and 70.4%, respectively. On univariate analysis, ASCA was significantly associated with younger age at diagnosis, ileal involvement, and complicated (stricturing/penetrating) behavior. On multivariate analysis, ASCA titer (per 25 Units) was associated with ileal involvement (OR 1.18, 95% confidence interval (CI): 1.04-1.34), complicated behavior (OR 1.13, 95% CI: 1.01-1.28), and surgery (hazard ratio: 1.11, 95% CI: 1.02-1.21). Cigarette smoking and CD family history were also significantly associated with surgery. NOD2 carriers (all heterozygotes) were more common among CD cases than controls (8.2 vs. 2.1%; OR 4.17%, 95% CI: 1.18-14.69). The NOD2 mutation population attributable risk was 6.2%. CONCLUSIONS: In comparison with whites, ASCA in AAs has a similar sensitivity but a lower specificity for CD. ASCA is associated with ileal involvement, complicated behavior, and surgery in AAs with CD. NOD2 is a risk gene for AA CD, although mutation frequency and population attributable risk are much lower than in whites.
OBJECTIVES:NOD2 mutations and anti-Saccharomyces cerevisiae antibodies (ASCAs) are established risk factors of Crohn's disease (CD) in whites but have not been assessed in African-American (AA) adults with CD. METHODS: AAs with CD and controls were recruited by the Mid-Atlantic African-American IBD Study as part of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium. Genotyping for the three common CDNOD2 mutations (Leu1007fsinsC, G908R/2722g>c, and R702W/2104c>t) and ASCA enzyme-linked immunosorbent assays were performed in 183 AA CDpatients and in 143 controls. Logistic regression was used to calculate adjusted odds ratios (ORs) for the association between ASCA and disease phenotype. RESULTS: ASCA sensitivity and specificity values were 70.5 and 70.4%, respectively. On univariate analysis, ASCA was significantly associated with younger age at diagnosis, ileal involvement, and complicated (stricturing/penetrating) behavior. On multivariate analysis, ASCA titer (per 25 Units) was associated with ileal involvement (OR 1.18, 95% confidence interval (CI): 1.04-1.34), complicated behavior (OR 1.13, 95% CI: 1.01-1.28), and surgery (hazard ratio: 1.11, 95% CI: 1.02-1.21). Cigarette smoking and CD family history were also significantly associated with surgery. NOD2 carriers (all heterozygotes) were more common among CD cases than controls (8.2 vs. 2.1%; OR 4.17%, 95% CI: 1.18-14.69). The NOD2 mutation population attributable risk was 6.2%. CONCLUSIONS: In comparison with whites, ASCA in AAs has a similar sensitivity but a lower specificity for CD. ASCA is associated with ileal involvement, complicated behavior, and surgery in AAs with CD. NOD2 is a risk gene for AA CD, although mutation frequency and population attributable risk are much lower than in whites.
Authors: Jochen Hampe; Jochen Grebe; Susanna Nikolaus; Camilla Solberg; Peter J P Croucher; Silvia Mascheretti; Jörgen Jahnsen; Björn Moum; Bodo Klump; Michael Krawczak; Muddassar M Mirza; Ulrich R Foelsch; Morten Vatn; Stefan Schreiber Journal: Lancet Date: 2002-05-11 Impact factor: 79.321
Authors: Steven R Brant; Michael F Picco; Jean-Paul Achkar; Theodore M Bayless; Sunanda V Kane; Aaron Brzezinski; Franklin J Nouvet; Denise Bonen; Amir Karban; Themistocles Dassopoulos; Reda Karaliukas; Terri H Beaty; Stephen B Hanauer; Richard H Duerr; Judy H Cho Journal: Inflamm Bowel Dis Date: 2003-09 Impact factor: 5.325
Authors: L J Walker; M C Aldhous; H E Drummond; B R K Smith; E R Nimmo; I D R Arnott; J Satsangi Journal: Clin Exp Immunol Date: 2004-03 Impact factor: 4.330
Authors: William S Mow; Eric A Vasiliauskas; Ying-Chao Lin; Phillip R Fleshner; Konstantinos A Papadakis; Kent D Taylor; Carol J Landers; Maria T Abreu-Martin; Jerome I Rotter; Huiying Yang; Stephan R Targan Journal: Gastroenterology Date: 2004-02 Impact factor: 22.682
Authors: Frank H Klebl; Frauke Bataille; Ferdinand Hofstädter; Hans Herfarth; Jürgen Schölmerich; Gerhard Rogler Journal: Int J Colorectal Dis Date: 2004-01-27 Impact factor: 2.571
Authors: T Heliö; L Halme; M Lappalainen; H Fodstad; P Paavola-Sakki; U Turunen; M Färkkilä; T Krusius; K Kontula Journal: Gut Date: 2003-04 Impact factor: 23.059
Authors: Peter J P Croucher; Silvia Mascheretti; Jochen Hampe; Klaus Huse; Henning Frenzel; Monika Stoll; Tim Lu; Susanna Nikolaus; Suk-Kyun Yang; Michael Krawczak; Won Ho Kim; Stefan Schreiber Journal: Eur J Hum Genet Date: 2003-01 Impact factor: 4.246
Authors: Maria T Abreu; Kent D Taylor; Ying-Chao Lin; Tieu Hang; Joanne Gaiennie; Carol J Landers; Eric A Vasiliauskas; Lori Y Kam; Micha Rojany; Konstantinos A Papadakis; Jerome I Rotter; Stephan R Targan; Huiying Yang Journal: Gastroenterology Date: 2002-09 Impact factor: 22.682
Authors: Madeline Bertha; Arthi Vasantharoopan; Archana Kumar; Beau B Bruce; Jarod Prince; Tatyana Hofmekler; David Okou; Pankaj Chopra; Gabriel Wang; Cary Sauer; Carol J Landers; Sunny Z Hussain; Raymond K Cross; Robert N Baldassano; Michael D Kappelman; Jeffrey Katz; Jonathan S Alexander; Barbara S Kirschner; Dedrick E Moulton; Bankole O Osuntokun; Ashish Patel; Shehzad Saeed; Jan-Michael A Klapproth; Tanvi A Dhere; Marla C Dubinsky; Dermot McGovern; Subra Kugathasan Journal: Inflamm Bowel Dis Date: 2017-12-19 Impact factor: 5.325
Authors: Ming-Hsi Wang; Toshihiko Okazaki; Subra Kugathasan; Judy H Cho; Kim L Isaacs; James D Lewis; Duane T Smoot; John F Valentine; Howard A Kader; Jean G Ford; Mary L Harris; Maria Oliva-Hemker; Carmen Cuffari; Michael S Torbenson; Richard H Duerr; Mark S Silverberg; John D Rioux; Kent D Taylor; Geoffrey C Nguyen; Yuqiong Wu; Lisa W Datta; Stanley Hooker; Themistocles Dassopoulos; Rick A Kittles; Linda W H Kao; Steven R Brant Journal: Inflamm Bowel Dis Date: 2012-03-12 Impact factor: 5.325