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PTPN2 gene variants are associated with susceptibility to both Crohn's disease and ulcerative colitis supporting a common genetic disease background.

التفاصيل البيبلوغرافية
العنوان: PTPN2 gene variants are associated with susceptibility to both Crohn's disease and ulcerative colitis supporting a common genetic disease background.
المؤلفون: Jürgen Glas, Johanna Wagner, Julia Seiderer, Torsten Olszak, Martin Wetzke, Florian Beigel, Cornelia Tillack, Johannes Stallhofer, Matthias Friedrich, Christian Steib, Burkhard Göke, Thomas Ochsenkühn, Nazanin Karbalai, Julia Diegelmann, Darina Czamara, Stephan Brand
المصدر: PLoS ONE, Vol 7, Iss 3, p e33682 (2012)
بيانات النشر: Public Library of Science (PLoS), 2012.
سنة النشر: 2012
المجموعة: LCC:Medicine
LCC:Science
مصطلحات موضوعية: Medicine, Science
الوصف: BACKGROUND: Genome-wide association studies identified PTPN2 (protein tyrosine phosphatase, non-receptor type 2) as susceptibility gene for inflammatory bowel diseases (IBD). However, the exact role of PTPN2 in Crohn's disease (CD) and ulcerative colitis (UC) and its phenotypic effect are unclear. We therefore performed a detailed genotype-phenotype and epistasis analysis of PTPN2 gene variants. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 2131 individuals of Caucasian origin (905 patients with CD, 318 patients with UC, and 908 healthy, unrelated controls) was analyzed for two SNPs in the PTPN2 region (rs2542151, rs7234029) for which associations with IBD were found in previous studies in other cohorts. Our analysis revealed a significant association of PTPN2 SNP rs2542151 with both susceptibility to CD (p = 1.95×10⁻⁵; OR 1.49 [1.34-1.79]) and UC (p = 3.87×10⁻², OR 1.31 [1.02-1.68]). Moreover, PTPN2 SNP rs7234029 demonstrated a significant association with susceptibility to CD (p = 1.30×10⁻³; OR 1.35 [1.13-1.62]) and a trend towards association with UC (p = 7.53×10⁻²; OR 1.26 [0.98-1.62]). Genotype-phenotype analysis revealed an association of PTPN2 SNP rs7234029 with a stricturing disease phenotype (B2) in CD patients (p = 6.62×10⁻³). Epistasis analysis showed weak epistasis between the ATG16L1 SNP rs2241879 and PTPN2 SNP rs2542151 (p = 0.024) in CD and between ATG16L1 SNP rs4663396 and PTPN2 SNP rs7234029 (p = 4.68×10⁻³) in UC. There was no evidence of epistasis between PTPN2 and NOD2 and PTPN2 and IL23R. In silico analysis revealed that the SNP rs7234029 modulates potentially the binding sites of several transcription factors involved in inflammation including GATA-3, NF-κB, C/EBP, and E4BP4. CONCLUSIONS/SIGNIFICANCE: Our data confirm the association of PTPN2 variants with susceptibility to both CD and UC, suggesting a common disease pathomechanism for these diseases. Given recent evidence that PTPN2 regulates autophagosome formation in intestinal epithelial cells, the potential link between PTPN2 and ATG16L1 should be further investigated.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1932-6203
Relation: http://europepmc.org/articles/PMC3310077?pdf=render; https://doaj.org/toc/1932-6203
DOI: 10.1371/journal.pone.0033682
URL الوصول: https://doaj.org/article/f79ea8e5a2864f5f9ee9cff83db30103
رقم الأكسشن: edsdoj.f79ea8e5a2864f5f9ee9cff83db30103
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:19326203
DOI:10.1371/journal.pone.0033682