Digesting the genetics of inflammatory bowel disease: Insights from studies of autophagy risk genes

Authors

  • Amrita Kabi PhD,

    1. Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
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  • Kourtney P. Nickerson BS,

    1. Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
    2. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio
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  • Craig R. Homer MS,

    1. Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
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  • Christine McDonald PhD

    Corresponding author
    1. Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
    2. Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio
    • Department of Pathobiology, NC22, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Ave., Cleveland, OH 44195
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  • Supported by a National Institutes of Health research grant (R01DK082437 to C.M.) and the Howard Hughes Medical Institute “Med Into Grad” initiative.

Abstract

The success of genetic analyses identifying multiple loci associated with inflammatory bowel disease (IBD) susceptibility has resulted in the identification of several risk genes linked to a common cellular process called autophagy. Autophagy is a process involving the encapsulation of cytosolic cellular components in double-membrane vesicles, their subsequent lysosomal degradation, and recycling of the degraded components for use by the cell. It plays an important part in the innate immune response to a variety of intracellular pathogens, and it is this component of autophagy that appears to be defective in IBD. This has lead to the hypothesis that Crohn's disease may result from an impaired antibacterial response, which leads to ineffective control of bacterial infection, dysbiosis of the intestinal microbiota, and chronic inflammation. Several recurrent themes have surfaced from studies examining the function of autophagy-related genes in the context of IBD, with cellular context, disease status, risk variant effect, and risk gene interplay all affecting the interpretation of these studies. The identification of autophagy as a major risk pathway in IBD is a significant step forward and may lead to pathway-focused therapy in the future; however, there is more to understand in order to unravel the complexity of this disease. (Inflamm Bowel Dis 2011;)

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