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

BMC Nephrology

Draga Toncheva⁷  Angel Galabov⁴  Valentin Djonov⁵  Ruslan Hlushchuk⁵  Ivanka Dimova⁷  Momir Polenakovic²  Vladislav Stefanovic⁶  Jovana Cukuranovic⁶  Rade Cukuranovic⁶  Georgi Stamenov¹  Valeri Simeonov⁸  Plamen Dimitrov³  Olga Antonova⁷  Desislava Nesheva⁷  Savina Hadjidekova⁷  Blaga Rukova⁷  Rada Staneva⁷ 

[1] Nadezhda Center for reproductive help, 3 Blaga Vest str, 1330 Sofia, Bulgaria;Macedonian Academy of Sciences and Arts, Bul. Krste Misirkov, 2, P.O. Box 428, 1000 Skopje, Republic of Macedonia;National Center of Public Health and Analyses, 15 Acad. Ivan Evst. Geshov blvd, 1431 Sofia, Bulgaria;Institute of Microbilogy, Bulgarian Academy of Sciences, 26 Georgi Bonchev str, 1113 Sofia, Bulgaria;Institute of Anatomy, Bern University, Baltzerstrasse 2, CH 3012 Bern, Switzerland;Faculty of Medicine, Institute of Nephrology, University of Nis, Univerzitetski trg 2, 18000 Nis, Serbia;Department of Medical Genetics, Medical University of Sofia, 1421 2Zdrave str, Sofia, Bulgaria;Vratza District Hospital, 66 “Vtori iuni” blvd, Vratza, Bulgaria

关键词: Balkan endemic nephropathy;    Whole genome array analysis;    Epigenetics;   

Others  :  1082814
DOI  :  10.1186/1471-2369-14-225

 received in 2013-04-15, accepted in 2013-10-11,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Staneva et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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