rs224136 on Chromosome 10q21.1 and Variants in PHOX2B, NCF4, and FAM92B Are Not Major Genetic Risk Factors for Susceptibility to ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2009-03

AUTHORS

Astrid Konrad, Bertram Müller-Myhsok, Burkhard Göke, Cornelia Tillack, Giulia Pasciuto, Helga-Paula Török, Jörg T Epplen, Jürgen Glas, Johannes Stallhofer, Julia Diegelmann, Julia Seiderer, Martin Wetzke, Matthias Folwaczny, Matthias Jürgens, Peter Lohse, Silke Schmechel, Simone Pfennig, Stephan Brand, Thomas Griga, Thomas Mussack, Thomas Ochsenkühn, Uwe Schiemann, Wolfram Klein

ABSTRACT

OBJECTIVES: Recently, a North American genome-wide association study identified three novel gene variants in PHOX2B, NCF4, and FAM92B as well as one single nucleotide polymorphisms (SNP; rs224136) in the intergenic region on chromosome 10q21.1 as being associated with Crohn's disease (CD). However, their influence on European CD patients as well as ulcerative colitis (UC) is unknown. Therefore we aimed to replicate these novel CD susceptibility variants in a large European cohort with inflammatory bowel disease and analyzed potential gene-gene interactions with variants in the NOD2/CARD15, IL23R, and ATG16L1 genes. METHODS: Genomic DNA from 2,833 Caucasian individuals including 854 patients with CD, 476 patients with UC, and 1,503 healthy unrelated controls was analyzed for SNPs in PHOX2B (rs16853571), NCF4 (rs4821544), and FAM92B (rs8050910), including rs224136 on chromosome 10q21.1. RESULTS: In our study population, no association of PHOX2B (P=0.563), NCF4 (P=0.506), FAM92B (P=0.401), and rs224136 (P=0.363) with CD was found. Similarly, none of these SNPs was associated with UC. In contrast, all analyzed SNPs in NOD2/CARD15, IL23R, and ATG16L1 were strongly associated with CD with P values ranging from 5.0x10(-3) to 1.6x10(-22), but there was no epistasis with polymorphisms in PHOX2B, NCF4, FAM92B, and rs224136. CONCLUSIONS: In contrast to the North American population, PHOX2B, NCF4, FAM92B, and rs224136 are not associated with CD in the European population, whereas NOD2/CARD15, IL23R, and ATG16L1 are strongly associated with CD in both the North American and European populations, confirming these three genes as major CD susceptibility genes in Caucasian populations. More... »

PAGES

665

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ajg.2008.65

    DOI

    http://dx.doi.org/10.1038/ajg.2008.65

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1009535465

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/19262523


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