دورية أكاديمية

RSPO4 is a potential risk gene of stages III-IV, grade C periodontitis through effects on innate immune response and oral barrier integrity.

التفاصيل البيبلوغرافية
العنوان: RSPO4 is a potential risk gene of stages III-IV, grade C periodontitis through effects on innate immune response and oral barrier integrity.
المؤلفون: Chopra A; Department of Periodontology, Oral Medicine and Oral Surgery, Institute for Dental and Craniofacial Sciences, Charité - University Medicine Berlin, Berlin, Germany., Song J; Department of Periodontology, Oral Medicine and Oral Surgery, Institute for Dental and Craniofacial Sciences, Charité - University Medicine Berlin, Berlin, Germany., Weiner J 3rd; Core Unit Bioinformatics, Berlin Institute of Health, Berlin, Germany., Keceli HG; Department of Periodontology, Faculty of Dentistry, Hacettepe University, Ankara, Turkey., Dincer PR; Faculty of Medicine, Department of Medical Biology, Hacettepe University, Ankara, Turkey., Cruz R; Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.; CIBERER-Instituto de Salud Carlos III, Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Carracedo A; Fundación Pública Galega de Medicina Xenómica, Instituto de Investigación Sanitaria de Santiago (IDIS), Santiago de Compostela, Spain.; CIBERER-Instituto de Salud Carlos III, Centro Singular de Investigación en Medicina Molecular y Enfermedades Crónicas (CIMUS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Blanco J; Grupo de Investigación en Odontología Médico-Quirúrgica (OMEQUI), Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Universidade de Santiago de Compostela, Santiago de Compostela, Spain., Dommisch H; Department of Periodontology, Oral Medicine and Oral Surgery, Institute for Dental and Craniofacial Sciences, Charité - University Medicine Berlin, Berlin, Germany., Schaefer AS; Department of Periodontology, Oral Medicine and Oral Surgery, Institute for Dental and Craniofacial Sciences, Charité - University Medicine Berlin, Berlin, Germany.
المصدر: Journal of clinical periodontology [J Clin Periodontol] 2023 Apr; Vol. 50 (4), pp. 476-486. Date of Electronic Publication: 2022 Dec 15.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 0425123 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-051X (Electronic) Linking ISSN: 03036979 NLM ISO Abbreviation: J Clin Periodontol Subsets: MEDLINE
أسماء مطبوعة: Publication: Malden, MA : Wiley-Blackwell
Original Publication: Copenhagen, Munksgaard.
مواضيع طبية MeSH: Alveolar Bone Loss* , Periodontitis*/genetics, Animals ; Mice ; Cell Adhesion Molecules, Neuronal ; Genotype ; Immunity, Innate/genetics ; Humans
مستخلص: Aim: R-spondin 4 (RSPO4) is a suggestive risk gene of stage III-IV, grade C periodontitis and upregulated in gingiva of mice resistant to bacteria-induced alveolar bone loss. We aimed to replicate the association, identify and characterize the putative causal variant(s) and molecular effects, and understand the downstream effects of RSPO4 upregulation.
Materials and Methods: We performed a two-step association study for RSPO4 with imputed genotypes of a German-Dutch (896 stage III-IV, grade C periodontitis cases, 7104 controls) and Spanish sample (441 cases and 1141 controls). We analysed the allelic effects on transcription factor binding sites with reporter gene and antibody electrophoretic mobility shift assays. We used CRISPR/dCas9 activation and RNA sequencing to pinpoint RSPO4 as the target gene and to analyse downstream effects.
Results: RSPO4 was associated with periodontitis (rs6056178, p meta  = 4.6 × 10 -5 ). rs6056178 contains a GATA-binding motif. The rs6056178 T-allele abolished reporter activity (p = .004) and reduced GATA binding (-14.5%). CRISPRa of the associated region increased RSPO4 expression (25.8 ± 6.5-fold, p = .003). RSPO4 activation showed strongest induction of Gliomedin (439-fold) and Mucin 21 (178-fold) and of the gene set "response to interferon-alpha" (area under the curve [AUC] = 0.8, p < 5 × 10 -6 ). The most repressed gene set was "extracellular matrix interactions" (AUC = 0.8, p adj  = .00016).
Conclusion: RSPO4 is a potential periodontitis risk gene and modifies host defence and barrier integrity.
(© 2022 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)
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فهرسة مساهمة: Keywords: GATA; GLDN; MUC21; causal variant; interferon alpha; rs6056178
المشرفين على المادة: 0 (Cell Adhesion Molecules, Neuronal)
0 (gliomedin protein, mouse)
0 (RSPO4 protein, human)
تواريخ الأحداث: Date Created: 20221212 Date Completed: 20230324 Latest Revision: 20230403
رمز التحديث: 20230404
DOI: 10.1111/jcpe.13758
PMID: 36507580
قاعدة البيانات: MEDLINE
الوصف
تدمد:1600-051X
DOI:10.1111/jcpe.13758