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Am J Gastroenterol. 2010 Feb;105(2):378-86. doi: 10.1038/ajg.2009.575. Epub 2009 Oct 13.

NOD2 mutations and anti-Saccharomyces cerevisiae antibodies are risk factors for Crohn's disease in African Americans.

Author information

1
Gastroenterology Division, Department of Medicine, The Harvey M. and Lyn P. Meyerhoff Inflammatory Bowel Disease Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. themos@im.wustl.edu

Abstract

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.

PMID:
19826411
PMCID:
PMC3339041
DOI:
10.1038/ajg.2009.575
[Indexed for MEDLINE]
Free PMC Article

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