title: FOXP3 DNA methylation levels as a potential biomarker in the development of periapical lesions.
abstract: BACKGROUND
  Epigenetic mechanisms, such as DNA methylation, can modify gene expression patterns without changing the DNA sequence, comprising a tool that cells use to lock genes in the "off" position. Variations in the methylation profile have been correlated to a variety of human diseases. Here, we hypothesize that DNA methylation in immune response-related genes may contribute to the development of periapical lesions.
  
  
  METHODS
  The DNA methylation patterns of 22 immune response-related gene promoters were evaluated in 137 human periapical granulomas, 8 apical cysts, and 31 healthy gingival tissues from 2 independent cohorts using a pathway-specific real-time polymerase chain reaction array (EpiTect Methyl II; Qiagen Inc, Valencia, CA). Messenger RNA expression analysis by qualitative polymerase chain reaction was also performed. SABiosciences's hierarchical clustering and methylation (Qiagen, Valencia, CA) and Prism6 software (GraphPad Software, Inc, La Jolla, CA) were used for data analysis.
  
  
  RESULTS
  FOXP3 gene promoter showed the highest level of methylation in both periapical granulomas and apical cysts (P < .001), and methylation levels were inversely correlated with FOXP3 messenger RNA expression in the lesions. Furthermore, FOXP3 expression was prevalent in inactive lesions and was positively correlated with interleukin-10 and transforming growth factor beta levels.
  
  
  CONCLUSIONS
  Our results suggest that FOXP3 acts as a master switch governing the development and function of T-regulatory cells, whose functions include the inhibition of immune responses and temper inflammation. The observed differential methylation patterns of FOXP3 in periapical lesions may be crucial in determining its suppressive activity and may be involved in periapical lesion development.
authors.affiliation: Department of Oral Surgery and Pathology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Kelma
authors.initials: K
authors.lastname: Campos
authors.affiliation: Department of Biological Sciences, School of Dentistry of Bauru, University of Sao Paulo, Bauru, São Paulo, Brazil.
authors.forename: Carolina F
authors.initials: CF
authors.lastname: Franscisconi
authors.affiliation: Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Valerie
authors.initials: V
authors.lastname: Okehie
authors.affiliation: Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Letícia C
authors.initials: LC
authors.lastname: de Souza
authors.affiliation: Department of Biological and Allied Health Sciences, Sacred Heart University, Bauru, Brazil.
authors.forename: Ana Paula F
authors.initials: AP
authors.lastname: Trombone
authors.affiliation: Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Ariadne
authors.initials: A
authors.lastname: Letra
authors.affiliation: Department of Biological Sciences, School of Dentistry of Bauru, University of Sao Paulo, Bauru, São Paulo, Brazil.
authors.forename: Gustavo P
authors.initials: GP
authors.lastname: Garlet
authors.affiliation: Department of Endodontics, School of Dentistry, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Ricardo S
authors.initials: RS
authors.lastname: Gomez
authors.affiliation: Department of Biological Sciences, School of Dentistry of Bauru, University of Sao Paulo, Bauru, São Paulo, Brazil. Electronic address: Renato.M.Silva@uth.tmc.edu.
authors.forename: Renato M
authors.initials: RM
authors.lastname: Silva
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005786:Gene Expression Regulation; D005881:Gingiva / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010482:Periapical Abscess / Q000235:genetics* / Q000473:pathology; D010484:Periapical Granuloma / Q000235:genetics* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
keywords: Apical periodontitis; DNA methylation; FOXP3