Gut Reactions

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Science  02 Dec 2005:
Vol. 310, Issue 5753, pp. 1391
DOI: 10.1126/science.310.5753.1391b

Celiac disease (CD) is caused by an immunological response to gluten peptides in wheat. This response damages the intestine and can compromise the absorption of essential nutrients. Specific variants of HLA class II genes (which encode proteins that participate in the immune recognition of gluten) confer an elevated risk of CD, but additional genes are likely to contribute to the disorder. Lifelong adherence to gluten-free diets is difficult, and there is interest in devising alternative therapies.

Promising new leads have emerged from genome-based studies of both the human victims and the plant assailant. In a genetic association analysis of two Dutch populations, Monsuur et al. identified a sequence variant that conferred a twofold greater risk of CD. This variant resides within an intron of the human MYO9B gene, which encodes an unconventional myosin that may play a role in the ability of intestinal epithelial cells to form a tight barrier, and the variant allele may increase the access of gluten peptides to immune cells. Spaenij-Dekking et al. investigated whether different varieties of wheat contain different levels of the gluten peptides that trigger the pathogenic immune reaction. Based on the results of database searches of gluten sequences and in vitro immunological assays, the authors concluded that sufficient genetic variation exists in wheat to warrant consideration of selection strategies that would produce varieties that are better tolerated by celiacs. — PAK

Nat. Genet. 10.1038/ng1680 (2005); Gastroenterology 129, 797 (2005).

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