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NOD2 and Crohn
Disease
Crohn disease usually begins in late
adolescence or early adulthood and follows an erratic course of
relapse and remission. Anti-inflammatory drugs (particularly
sulfasalazine and glucocorticoids) are mainstays for preventing
and managing intermittent exacerbations. Antibiotics are often
used empirically, but few controlled studies have been conducted
to evaluate their efficacy. Although surgery is eventually
necessary in most patients, it is not curative. People with
Crohn disease have near-normal life expectancy, but the early onset
of illness, severe complications, and side effects of long-term
therapy produce significant morbidity. Factors in the etiology and pathogenesis of Crohn disease have remained frustratingly obscure despite 50 years of clinical and laboratory investigation. Epidemiologic studies suggest a role for environmental factors (such as diet, smoking, infectious agents, stress, higher socioeconomic status, and geography) and regularly demonstrate family clustering, although without a clear pattern of inheritance. Thus, Crohn disease is thought to result from a complex interaction between genetic susceptibility and environmental exposures. Recent advances in molecular biology have intensified the search for genetic factors and pathogenetic mechanisms in Crohn disease and ulcerative colitis. In 1996, Hugot et al. reported the results of a genome-wide linkage analysis that identified a susceptibility region on chromosome 16, which they termed IBD1. In 2001, Ogura et al. identified the NOD2 gene, mapped it to chromosome 16q12, and demonstrated that it activated nuclear factor kappa B (NF-kB), a component of the innate immune response.
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last updated August 09, 2004 |