Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology

Staneva, Rada; Rukova, Blaga; Hadjidekova, Savina; Nesheva, Desislava; Antonova, Olga; Dimitrov, Plamen; Simeonov, Valeri; Stamenov, Georgi; Cukuranovic, Rade; Cukuranovic, Jovana; Stefanovic, Vladislav; Polenakovic, Momir; Dimova, Ivanka; Hlushchuk, Ruslan; Djonov, Valentin; Galabov, Angel; Toncheva, Draga (2013). Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology. BMC nephrology, 14(1), p. 225. BioMed Central 10.1186/1471-2369-14-225

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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. Conclusion Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis. Keywords: Epigenetics; Whole genome array analysis; Balkan endemic nephropathy

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Dimova, Ivanka; Hlushchuk, Ruslan and Djonov, Valentin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1471-2369

Publisher:

BioMed Central

Language:

English

Submitter:

Beatrice Itten

Date Deposited:

04 Apr 2014 19:09

Last Modified:

08 Dec 2014 20:13

Publisher DOI:

10.1186/1471-2369-14-225

PubMed ID:

24131581

Uncontrolled Keywords:

Epigenetics, Whole genome array analysis, Balkan endemic nephropathy

BORIS DOI:

10.7892/boris.39400

URI:

https://boris.unibe.ch/id/eprint/39400

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