title: Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology.
abstract: BACKGROUND
  Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries.DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood.
  
  
  METHODS
  We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian endemic regions.
  
  
  RESULTS
  Using specifically developed software we compared the methylation profiles of BEN patients and corresponding controls and revealed the differently methylated regions. We then compared the DMRs between all patient-control pairs to determine common changes in the epigenetic profiles.SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs. The CpG islands of all 3 genes were hypomethylated compared to controls. This suggests that dysregulation of these genes involved in immunological response could be a common mechanism in BEN pathogenesis in both endemic regions and in both genders.
  
  
  CONCLUSIONS
  Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis.
authors.forename: Rada
authors.initials: R
authors.lastname: Staneva
authors.forename: Blaga
authors.initials: B
authors.lastname: Rukova
authors.forename: Savina
authors.initials: S
authors.lastname: Hadjidekova
authors.forename: Desislava
authors.initials: D
authors.lastname: Nesheva
authors.forename: Olga
authors.initials: O
authors.lastname: Antonova
authors.forename: Plamen
authors.initials: P
authors.lastname: Dimitrov
authors.forename: Valeri
authors.initials: V
authors.lastname: Simeonov
authors.forename: Georgi
authors.initials: G
authors.lastname: Stamenov
authors.forename: Rade
authors.initials: R
authors.lastname: Cukuranovic
authors.forename: Jovana
authors.initials: J
authors.lastname: Cukuranovic
authors.forename: Vladislav
authors.initials: V
authors.lastname: Stefanovic
authors.forename: Momir
authors.initials: M
authors.lastname: Polenakovic
authors.forename: Ivanka
authors.initials: I
authors.lastname: Dimova
authors.forename: Ruslan
authors.initials: R
authors.lastname: Hlushchuk
authors.forename: Valentin
authors.initials: V
authors.lastname: Djonov
authors.forename: Angel
authors.initials: A
authors.lastname: Galabov
authors.affiliation: Department of Medical Genetics, Medical University of Sofia, 1421 2Zdrave str, Sofia, Bulgaria. dragatoncheva@gmail.com.
authors.forename: Draga
authors.initials: D
authors.lastname: Toncheva
mesh_terms: D000368:Aged; D001449:Balkan Nephropathy / Q000453:epidemiology* / Q000235:genetics*; D063368:Balkan Peninsula / Q000453:epidemiology; D002031:Bulgaria / Q000453:epidemiology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D019353:Endemic Diseases / Q000706:statistics & numerical data*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D055771:Serbia / Q000453:epidemiology