title: Analysis of MEFV exon methylation and expression patterns in familial Mediterranean fever.
abstract: BACKGROUND
  MEFV mutations and decreased expression level of the gene are related to FMF pathology. DNA methylation at CpG islands is a well-known mechanism for transcriptional silencing. MEFV has a CpG island, spanning a part of the first intron and the whole of the second exon of the gene covering 998 bp region. Here, we tested the hypothesis that the MEFV transcript level in FMF patients correlates with its methylation level, and methylation, by allowing transcription silencing, has a role in FMF ethiopathogenesis.
  
  
  METHODS
  The study group was composed of pediatric FMF patients (N = 51) and age-gender matched healthy controls (N = 21). The relative expression level of MEFV was assessed via quantitative real-time PCR (qRT-PCR) and bisulfite sequencing (BS) was performed to analyse the methylation level quantitatively.
  
  
  RESULTS
  MEFV expression in FMF patients were decreased compared to healthy controls (P = 0.031). Methylation level of exon 2 of MEFV was found to be slightly higher in FMF patients compared to healthy controls (76% versus 74%) (P = 0.049). The expression level of the MEFV was negatively correlated with the methylation level of the CpG island in both FMF and healthy controls groups (cor = -0.29, P = 0.041) but more so in the FMF only group (cor = -0.36, P = 0.035).
  
  
  CONCLUSIONS
  In this study, the relation between reduced MEFV expression level and FMF was confirmed. Observed slight increase in methylation in FMF patients, and correlation of methylation with expression might be indicative of its role in FMF, however a larger dataset is needed to confirm our preliminary findings.
authors.affiliation: Institute of Science and Technology, Molecular Biology Genetics and Biotechnology Graduate Program, Istanbul Technical University, Istanbul, Turkey.
authors.forename: Asli K
authors.initials: AK
authors.lastname: Kirectepe
authors.forename: Ozgur
authors.initials: O
authors.lastname: Kasapcopur
authors.forename: Nil
authors.initials: N
authors.lastname: Arisoy
authors.forename: Gokce
authors.initials: G
authors.lastname: Celikyapi Erdem
authors.forename: Gulen
authors.initials: G
authors.lastname: Hatemi
authors.forename: Huri
authors.initials: H
authors.lastname: Ozdogan
authors.forename: Eda
authors.initials: E
authors.lastname: Tahir Turanli
mesh_terms: D000293:Adolescent; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics*; D010505:Familial Mediterranean Fever / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D005787:Gene Frequency; D006801:Humans; D008297:Male; D000071198:Pyrin; D054928:Validation Studies as Topic
chemical_list: D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin