title: Genetic, Genomic and Epigenomic Studies of Balkan Endemic Nephropathy (Ben).
abstract: BEN is a primary, chronic tubulointerstitial nephritis characterized with chronic anemia, absence of edema, xantoderma, normal blood pressure and normal findings on the fundus oculi. The disease is distributed in restricted areas in Bulgaria, Romania, Croatia, Bosnia, Former Yugoslavia. Despite numerous studies on genetic and environmental factors and their possible involvement in BEN, its etiopathogenesis still remains elusive. Our recent study aim to elucidate the possible epigenetic component in BEN development. Whole genome DNA array methylation analysis was applied to compare the methylation profiles of male and female BEN patients from endemic regions in Bulgaria and Serbia and healthy controls. All three most prominent candidate genes with aberrations in the epigenetic profile discovered with this study are involved in the inflammatory/immune processes and oncogenesis. These data are in concordance with the reported pathological alterations in BEN. This research supports the role of epigenetic changes in BEN pathology. Exome sequencing of 22.000 genes with Illumina Nextera Exome Enrichment Kit revealed three mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients which encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN.
authors.forename: Rada G
authors.initials: RG
authors.lastname: Staneva
authors.forename: L
authors.initials: L
authors.lastname: Balabanski
authors.forename: I
authors.initials: I
authors.lastname: Dimova
authors.forename: B
authors.initials: B
authors.lastname: Rukova
authors.forename: S
authors.initials: S
authors.lastname: Hadjidekova
authors.forename: P
authors.initials: P
authors.lastname: Dimitrov
authors.forename: V
authors.initials: V
authors.lastname: Simeonov
authors.forename: S
authors.initials: S
authors.lastname: Ivanov
authors.forename: R
authors.initials: R
authors.lastname: Vagarova
authors.forename: M
authors.initials: M
authors.lastname: Malinov
authors.forename: R
authors.initials: R
authors.lastname: Cukuranovic
authors.forename: V
authors.initials: V
authors.lastname: Stefanovic
authors.forename: M
authors.initials: M
authors.lastname: Polenakovic
authors.forename: V
authors.initials: V
authors.lastname: Djonov
authors.forename: A
authors.initials: A
authors.lastname: Galabov
authors.forename: D
authors.initials: D
authors.lastname: Toncheva
mesh_terms: D001449:Balkan Nephropathy / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D002031:Bulgaria / Q000453:epidemiology; D016022:Case-Control Studies; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D059472:Exome; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D023281:Genomics / Q000379:methods; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D010196:Pancreatic Elastase / Q000235:genetics; D010641:Phenotype; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics; D012307:Risk Factors; D055771:Serbia / Q000453:epidemiology
chemical_list: D005819:Genetic Markers; D019812:Heparan Sulfate Proteoglycans; C410295:KCNK5 protein, human; D024683:Potassium Channels, Tandem Pore Domain; C071927:perlecan; C000595173:CELA1 protein, human; D010196:Pancreatic Elastase