<abstract xmlns="http://www.w3.org/1999/xhtml"> 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. </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.

Genetic, Genomic and Epigenomic Studies of Balkan Endemic Nephropathy (Ben)

Department of Medical Genetics, Medical University of Sofia, 1421 2 Zdrave str, Sofia, Bulgaria

National Center of Public Health and Analyses, 15 Acad. Ivan Evst. Geshov blvd, 1431 Sofia, Bulgaria

Vratza District Hospital, 66 "Vtori iuni" blvd, Vratza, Bulgaria

Faculty of Medicine, Institute of Nephrology, University of Nis, Univerzitetski trg 2, 18000 Nis, Serbia

Macedonian Academy of Sciences and Arts, Bul. Krste Misirkov, 2, P.O. Box 428, 1000 Skopje, Republic of Macedonia

Institute of Anatomy, Bern University, Baltzerstrasse 2, CH 3012 Bern, Switzerland

Institute of Microbilogy, Bulgarian Academy of Sciences, 26 Georgi Bonchev str, 1113 Sofia, Bulgaria

PRILOZI

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

{"article-title":"Genetic, Genomic and Epigenomic Studies of Balkan Endemic Nephropathy (Ben)"}

BEN is a primary, chronic tubulointerstitial nephritis characterized with chronic anemia, absence of edema, xantoderma, normal blood pressure and normal...

Genetic, Genomic and Epigenomic Studies of Balkan Endemic Nephropathy (Ben)

Publicado en línea: 30 dic 2015

Páginas: 101 - 108

DOI: https://doi.org/10.1515/prilozi-2015-0058

Palabras clave
next generation sequencing (NGS), exome sequencing, methylation analysis, gene mutations, single nucleotide polymorphisms, Balkan Endemic Nephropathy

© 2016

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Genetic, Genomic and Epigenomic Studies of Balkan Endemic Nephropathy (Ben)

Publicado en línea: 30 dic 2015

Páginas: 101 - 108

DOI: https://doi.org/10.1515/prilozi-2015-0058

Palabras clavenext generation sequencing (NGS), exome sequencing, methylation analysis, gene mutations, single nucleotide polymorphisms, Balkan Endemic Nephropathy

© 2016

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Palabras clave
next generation sequencing (NGS), exome sequencing, methylation analysis, gene mutations, single nucleotide polymorphisms, Balkan Endemic Nephropathy