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IL-23 receptor (IL-23R) gene protects against pediatric Crohn's disease

Authors

  • Marla C. Dubinsky MD,

    Corresponding author
    1. Departments of Pediatrics, Medicine, and Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
    • 8700 Beverly Boulevard, Suite 1165W, Los Angeles CA 90048
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  • Dai Wang PhD,

    1. Departments of Pediatrics, Medicine, and Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
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  • Yoana Picornell,

    1. Departments of Pediatrics, Medicine, and Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
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  • Iwona Wrobel MD,

    1. Department of Pediatrics at participating institutions of the Western Regional Research Alliance for Pediatric IBD: Alberta Children's Hospital, Calgary, Canada
    2. University of California Davis Medical Center, Sacramento, California
    3. Seattle Children's Hospital, Seattle, Washington
    4. Phoenix Children's Hospital, Phoenix, Arizona
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  • Lirona Katzir,

    1. Departments of Pediatrics, Medicine, and Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
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  • Antonio Quiros MD,

    1. Department of Pediatrics at participating institutions of the Western Regional Research Alliance for Pediatric IBD: Alberta Children's Hospital, Calgary, Canada
    2. University of California Davis Medical Center, Sacramento, California
    3. Seattle Children's Hospital, Seattle, Washington
    4. Phoenix Children's Hospital, Phoenix, Arizona
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  • Debra Dutridge,

    1. Departments of Pediatrics, Medicine, and Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
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  • Ghassan Wahbeh MD,

    1. Department of Pediatrics at participating institutions of the Western Regional Research Alliance for Pediatric IBD: Alberta Children's Hospital, Calgary, Canada
    2. University of California Davis Medical Center, Sacramento, California
    3. Seattle Children's Hospital, Seattle, Washington
    4. Phoenix Children's Hospital, Phoenix, Arizona
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  • Gary Silber MD,

    1. Department of Pediatrics at participating institutions of the Western Regional Research Alliance for Pediatric IBD: Alberta Children's Hospital, Calgary, Canada
    2. University of California Davis Medical Center, Sacramento, California
    3. Seattle Children's Hospital, Seattle, Washington
    4. Phoenix Children's Hospital, Phoenix, Arizona
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  • Ron Bahar MD,

    1. Departments of Pediatrics, Medicine, and Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
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  • Emebet Mengesha,

    1. Departments of Pediatrics, Medicine, and Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
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  • Stephan R. Targan MD,

    1. Departments of Pediatrics, Medicine, and Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
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  • Kent D. Taylor PhD,

    1. Departments of Pediatrics, Medicine, and Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
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  • Jerome I. Rotter MD

    1. Departments of Pediatrics, Medicine, and Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California
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Abstract

Background: The IL-23 receptor (IL-23R) has been found to be associated with small bowel Crohn's disease (CD) in a whole genome association study. Specifically, the rare allele of the R381Q single nucleotide polymorphism (SNP) conferred protection against CD. It is unknown whether IL-23R is associated with IBD in children. The aim was to examine the association of IL-23R with susceptibility to IBD in pediatric patients.

Methods: DNA was collected from 609 subjects (151 CD and 52 ulcerative colitis [UC] trios). Trios were genotyped for the R381Q SNP of the IL-23R gene and SNP8, SNP12, SNP13, of the CARD15 gene using Taqman. The transmission disequilibrium test (TDT) was used for association to disease using GENEHUNTER 2.0.

Results: The rare allele of R381Q SNP was present in 2.7% of CD and 2.9% UC probands. The CARD15 frequency was 31.5% (CD) and 18% (UC). The IL-23R allele was negatively associated with inflammatory bowel disease (IBD): the R381Q SNP was undertransmitted in children with IBD (8 transmitted [T] versus 27 untransmitted [UT]; P = 0.001). This association was significant for all CD patients (6 T versus 19 UT; P = 0.009), especially for non-Jewish CD patients (2 T versus 17 UT; P = 0.0006). TDT showed a borderline association for UC (2 T versus 8 UT; P = 0.06). As expected, CARD15 was associated with CD in children by the TDT (58 T versus 22 UT P = 0.00006), but not with UC.

Conclusions: The protective IL-23R R381Q variant was particularly associated with CD in non-Jewish children. Thus, the initial whole genome association study based on ileal CD in adults has been extended to the pediatric population and beyond small bowel CD.

(Inflamm Bowel Dis 2007)

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