title: Association of CXCL12 gene promoter methylation with periodontitis in patients with diabetes mellitus type 2.
abstract: OBJECTIVE
  CXCL12 is widely expressed, constitutive chemokine involved in tissue repair and regeneration, while the extent of its expression is important in various chronic inflammatory conditions. Involvement of DNA methylation in CXCL12 gene suppression (CXCL12) has been shown in malignancy and some autoimmune diseases. The aim of this study was to investigate whether the alterations in DNA methylation of CXCL12 are also involved in progression of periodontitis in combination with diabetes, as these chronic inflammatory conditions are strongly interrelated.
  
  
  METHODS
  Study included 72 subjects divided in three groups: healthy control (C, n=21), periodontitis (P, n=29) and diabetes/periodontitis group (D/P, n=22). DNA extracted from epithelial cells obtained by sterile cotton swabs from buccal mucosa was subjected to methylation specific polymerase chain reaction (MSP) to obtain DNA methylation pattern of CXCL12 promoter.
  
  
  RESULTS
  CXCL12 promoter was predominantly unmethylated in all groups. However, increase in the frequency of the methylated form and increase in percent of methylation of CXCL12 promoter in periodontitis and diabetes/periodontitis group compared to control group were found, although without statistical significance. However, statistically significant increase in Tm of MSP products in diabetes/periodontitis group was observed. Correlation analysis revealed statistically significant relationship between the extent of DNA methylation of the CXCL12 promoter and periodontal parameters, as well as between DNA methylation of CXCL12 and glycosylated hemoglobin.
  
  
  CONCLUSIONS
  Presented results suggest that chronic inflammation contributes to the change of CXCL12 DNA methylation in buccal cells and that DNA methylation profile of CXCL12 promoter plays important role in development and progression of periodontal disease.
authors: Institute for Biological Research "Siniša Stanković", Department of Molecular Biology, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors: Nevena
authors: N
authors: Grdović
authors: Institute for Biological Research "Siniša Stanković", Department of Molecular Biology, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors: Jovana
authors: J
authors: Rajić
authors: Department of Periodontology and Oral Medicine, School of Dental Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.
authors: Sanja Matić
authors: SM
authors: Petrović
authors: Institute for Biological Research "Siniša Stanković", Department of Molecular Biology, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors: Svetlana
authors: S
authors: Dinić
authors: Institute for Biological Research "Siniša Stanković", Department of Molecular Biology, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors: Aleksandra
authors: A
authors: Uskoković
authors: Institute for Biological Research "Siniša Stanković", Department of Molecular Biology, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors: Mirjana
authors: M
authors: Mihailović
authors: Institute for Biological Research "Siniša Stanković", Department of Molecular Biology, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors: Jelena Arambašić
authors: JA
authors: Jovanović
authors: Institute for Biological Research "Siniša Stanković", Department of Molecular Biology, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
authors: Anja
authors: A
authors: Tolić
authors: Department of Periodontology and Oral Medicine, School of Dental Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.
authors: Ana
authors: A
authors: Pucar
authors: Institute of Human Genetics, School of Dental Medicine, University of Belgrade, Dr Subotica 8, 11000 Belgrade, Serbia.
authors: Jelena
authors: J
authors: Milašin
authors: Institute for Biological Research "Siniša Stanković", Department of Molecular Biology, University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia. Electronic address: melita@ibiss.bg.ac.rs.
authors: Melita
authors: M
authors: Vidaković
mesh_terms: D000328:Adult; D054377:Chemokine CXCL12 / Q000235:genetics*; D055113:Chronic Periodontitis / Q000235:genetics*; D003430:Cross-Sectional Studies; D019175:DNA Methylation / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D006442:Glycated Hemoglobin / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D055771:Serbia; D011795:Surveys and Questionnaires
chemical_list: D054377:Chemokine CXCL12; D006442:Glycated Hemoglobin; C515255:CXCL12 protein, human
keywords: Buccal cells; CXCL12; DNA methylation; Diabetes; Periodontitis