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Genetic Association of Nonsynonymous Variants of the IL23R with Familial and Sporadic Inflammatory Bowel Disease in Women

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Abstract

Purpose To replicate the association of IL23R R381Q (rs11209026) with inflammatory bowel disease (IBD), examine the effect of the two nonsynonymous variations, Q3H and L310P, on IBD, and to study gender distribution of these variants in IBD patients. Results IL23R R381Q was associated with Crohn’s disease (CD) (P = 0.010), but not with ulcerative colitis (UC); L310P was associated with UC (P = 0.004), but not with CD; no association was observed for Q3H with CD or UC. A female-specific association of R381Q with CD (P = 0.041), and of L310P with UC (P = 0.008) was observed. Conclusion We replicated the association of IL23R R381Q with CD but not UC, and we observed an association of L310P with UC, but not CD, in a central Pennsylvania population. Further analysis of the distribution of IL23R variants revealed that these effects were largely female-specific. The results suggest that IL23R R381Q confers protection against CD and that L310P confers protection against UC in females.

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Acknowledgments

This work is supported by a grant from the Philadelphia Health Care Trust (WAK), a Research Grant from the Barsumian Trust, Pennsylvania State University, College of Medicine (NJT), and a Research Fellowship from Alexander von Humboldt Foundation (ZL). The authors thank Rainer Vogler, Catharina Fuerstenau, Birthe Fedders, Tanja Wesse, Tanja Henke, and Lena Bossen for help with SNPlex genoty**, Tony Lin for his assistance with RFLP genoty**, Kimberly Walker, John Hegarty, and Gaylene Webber for their help in manuscript preparation. The authors gratefully acknowledge the Gift of Life Donor Program (Philadelphia, PA) and the generosity of the organ donor families for allowing these organs that are not suitable for transplantation to be utilized to advance the understanding of human disease.

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Authors and Affiliations

  1. Department of Surgery, College of Medicine, The Pennsylvania State University, 500 University Drive, H 137, Hershey, PA, 17033, USA

    Zhenwu Lin, Lisa Poritz, Kathryn A. Byrnes, Yunhua Wang, Anthony W. Gebhard & Walter A. Koltun

  2. Institute for Clinical Molecular Biology, Christian-Albrechts-University, Kiel, Germany

    Andre Franke, Andreas Ruether & Stefan Schreiber

  3. Total Health Management and Technology, Inc, Philadelphia, PA, USA

    Tong-Yi Li

  4. Obstetrics and Gynecology, College of Medicine, The Pennsylvania State University, Hershey, PA, USA

    Colin MacNeill

  5. Department of Pediatrics, College of Medicine, The Pennsylvania State University, Hershey, PA, USA

    Neal J. Thomas

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Lin, Z., Poritz, L., Franke, A. et al. Genetic Association of Nonsynonymous Variants of the IL23R with Familial and Sporadic Inflammatory Bowel Disease in Women. Dig Dis Sci 55, 739–746 (2010). https://doi.org/10.1007/s10620-009-0782-8

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