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A two-marker haplotype in the IRF5 gene is associated with inflammatory bowel disease in a North American cohort

Genes & Immunity volume 13, pages 351–355 (2012)Cite this article

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Abstract

Interferon regulatory factor 5 (IRF5) located on human chromosome 7q32 is associated with many chronic inflammatory disorders. IRF5 is the key regulator of proinflammatory cytokines and type I interferons. We surveyed two cohorts of inflammatory bowel disease (IBD) patients from a North American Consortium. Six single-nucleotide polymorphisms and a 5-base-pair (bp) insertion–deletion (CGGGG indel)polymorphism were investigated. Cytokine secretion was measured in primary lymphocytes after toll-like receptor 9 stimulation. Two-marker haplotypes containing the pairs (rs4728142–CGGGG indel) and (CGGGG indel–rs7808907) were associated with IBD protection (P=2.89 × 10−6, P=9.32 × 10−4 (non-Jewish ancestry) and P=4.68 × 10−8, P=2.50 × 10−8 (Jewish ancestry)) and IBD risk (P=0.004, P=0.003 (Jewish ancestry), respectively. IRF5 polymorphisms were risk factors for IBD in a single cohort. Interleukin-12-p70 cytokine production was higher (P=0.04) in lymphocytes from controls with two alleles of the 5-bp insertion. IRF5 polymorphisms contribute to the risk profile for Crohn's disease and ulcerative colitis along with ancestry and NOD2 genotypes.

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Acknowledgements

We thank Evelyn Ng for her skillful technical assistance. We are also greatful to Yashoda Sharma and other members of the NIDDK IBD genetics consortium for assistance with the clinical database. This work was supported by the following grants from the National Institutes of Health: T32 DK 07017 30 and U01 DK 062422-08 S1.

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Authors and Affiliations

  1. Department of Pediatrics,

    G Gathungu

  2. , Stony Brook Medical Center, Stony Brook, NY, USA

    G Gathungu

  3. Keck Biotechnology Laboratory, Yale School of Medicine, New Haven, CT, USA

    C K Zhang

  4. Department of Internal Medicine, Division of Digestive Disease, Yale School of Medicine, New Haven, CT, USA

    C K Zhang, W Zhang & J H Cho

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  1. G Gathungu
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  2. C K Zhang
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  4. J H Cho
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Correspondence to G Gathungu.

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Gathungu, G., Zhang, C., Zhang, W. et al. A two-marker haplotype in the IRF5 gene is associated with inflammatory bowel disease in a North American cohort. Genes Immun 13, 351–355 (2012). https://doi.org/10.1038/gene.2011.90

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