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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. CONCLUSION: Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis.

SUBMITTER: Staneva R

PROVIDER: S-EPMC3852817 | biostudies-other | 2013

REPOSITORIES: biostudies-other

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

Staneva Rada R Rukova Blaga B Hadjidekova Savina S Nesheva Desislava D Antonova Olga O Dimitrov Plamen P Simeonov Valeri V Stamenov Georgi G Cukuranovic Rade R Cukuranovic Jovana J Stefanovic Vladislav V Polenakovic Momir M Dimova Ivanka I Hlushchuk Ruslan R Djonov Valentin V Galabov Angel A Toncheva Draga D

BMC nephrology 20131016

<h4>Background</h4>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, c ...[more]

PMID: 24131581

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Project description:ImportanceUnderstanding the causes of infant mortality shapes public health, surveillance, and research investments. However, the association of single-locus (mendelian) genetic diseases with infant mortality is poorly understood.ObjectiveTo determine the association of genetic diseases with infant mortality.Design, setting, and participantsThis cohort study was conducted at a large pediatric hospital system in San Diego County (California) and included 546 infants (112 infant deaths [20.5%] and 434 infants [79.5%] with acute illness who survived; age, 0 to 1 year) who underwent diagnostic whole-genome sequencing (WGS) between January 2015 and December 2020. Data analysis was conducted between 2015 and 2022.ExposureInfants underwent WGS either premortem or postmortem with semiautomated phenotyping and diagnostic interpretation.Main outcomes and measuresProportion of infant deaths associated with single-locus genetic diseases.ResultsAmong 112 infant deaths (54 girls [48.2%]; 8 [7.1%] African American or Black, 1 [0.9%] American Indian or Alaska Native, 8 [7.1%] Asian, 48 [42.9%] Hispanic, 1 [0.9%] Native Hawaiian or Pacific Islander, and 34 [30.4%] White infants) in San Diego County between 2015 and 2020, single-locus genetic diseases were the most common identifiable cause of infant mortality, with 47 genetic diseases identified in 46 infants (41%). Thirty-nine (83%) of these diseases had been previously reported to be associated with childhood mortality. Twenty-eight death certificates (62%) for 45 of the 46 infants did not mention a genetic etiology. Treatments that can improve outcomes were available for 14 (30%) of the genetic diseases. In 5 of 7 infants in whom genetic diseases were identified postmortem, death might have been avoided had rapid, diagnostic WGS been performed at time of symptom onset or regional intensive care unit admission.Conclusions and relevanceIn this cohort study of 112 infant deaths, the association of genetic diseases with infant mortality was higher than previously recognized. Strategies to increase neonatal diagnosis of genetic diseases and immediately implement treatment may decrease infant mortality. Additional study is required to explore the generalizability of these findings and measure reduction in infant mortality.

Dataset Information

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

Publications

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

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