Dataset Information

A genome-wide methylation study on essential hypertension in young African American males.

ABSTRACT:

Objective

There is emerging evidence from animal studies suggesting a key role for methylation in the pathogenesis of essential hypertension. However, to date, very few studies have investigated the role of methylation in the development of human hypertension, and none has taken a genome-wide approach. Based on the recent studies that highlight the involvement of inflammation in the development of hypertension, we hypothesize that changes in DNA methylation of leukocytes are involved in the pathogenesis of hypertension.

Method & results

We conducted a genome-wide methylation analysis on 8 hypertensive cases and 8 normotensive age-matched controls aged 14-23 years and performed validation of the most significant CpG sites in 2 genes in an independent sample of 36 hypertensive cases and 60 normotensive controls aged 14-30 years. Validation of the CpG sites in the SULF1 gene was further conducted in a second replication sample of 36 hypertensive cases and 34 controls aged 15.8-40 years. A CpG site in the SULF1 gene showed higher methylation levels in cases than in healthy controls in the genome-wide step (p?=?6.2×10(-5)), which was confirmed in the validation step (p?=?0.011) for subjects ?30 years old but was not significant for subjects of all ages combined (p?=?0.095).

Conclusion

The identification of a difference in a blood leukocyte DNA methylation site between hypertensive cases and normotensive controls suggests that changes in DNA methylation may play an important role in the pathogenesis of hypertension. The age dependency of the effect further suggests complexity of epigenetic regulation in this age-related disease.

SUBMITTER: Wang X

PROVIDER: S-EPMC3542324 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

A genome-wide methylation study on essential hypertension in young African American males.

Wang Xiaoling X Falkner Bonita B Zhu Haidong H Shi Huidong H Su Shaoyong S Xu Xiaojing X Sharma Ashok Kumar AK Dong Yanbin Y Treiber Frank F Gutin Bernard B Harshfield Gregory G Snieder Harold H

PloS one 20130110 1

<h4>Objective</h4>There is emerging evidence from animal studies suggesting a key role for methylation in the pathogenesis of essential hypertension. However, to date, very few studies have investigated the role of methylation in the development of human hypertension, and none has taken a genome-wide approach. Based on the recent studies that highlight the involvement of inflammation in the development of hypertension, we hypothesize that changes in DNA methylation of leukocytes are involved in ...[more]

PMID: 23325143

Similar Datasets

Project description:Exposure to violence (ETV) has been linked to epigenomics mechanisms such as DNA methylation (DNAm). We used epigenetic profiling of blood collected from 32 African American young adult males who lived in Washington DC to determine if changes in DNAm at CpG sites affiliated with nervous and immune system were associated with exposure to violence. Pathway analysis of differentially methylated regions comparing high and low ETV groups revealed an enrichment of gene sets annotated to nervous system and immune ontologies. Many of these genes are known to interact with each other which suggests DNAm alters gene function in the nervous and immune system in response to ETV. Using data from a unique age group, young African American adult males, we provide evidence that lifetime ETV could impact DNA methylation in genes impacted at Central Nervous System and Immune Function sites.MethodMethylation analysis was performed on DNA collected from the blood of participants classified with either high or low lifetime ETV. Illumina®MethylationEPIC Beadchips (~850k CpG sites) were processed on the iScan System to examine whole-genome methylation differences. Differentially methylated CpG-sites between high (n = 19) and low (n = 13) groups were identified using linear regression with violence and substance abuse as model covariates. Gene ontology analysis was used to identify enrichment categories from probes annotated to the nearest gene.ResultsA total of 595 probes (279 hypermethylated; 316 hypomethylated) annotated to 383 genes were considered differentially methylated in association with ETV. Males with high ETV showed elevated methylation in several signaling pathways but were most impacted at Central Nervous System and Immune Function affiliated sites. Eight candidate genes were identified that play important biological roles in stress response to violence with HDAC4 (10%), NR4A3 (11%), NR4A2 (12%), DSCAML1(12%), and ELAVL3 (13%) exhibiting higher levels in the low ETV group and DLGAP1 (10%), SHANK2 (10%), and NRG1(11%) having increased methylation in the high ETV group. These findings suggest that individuals subjected to high ETV may be at risk for poor health outcomes that have not been reported previously.

Dataset Information

A genome-wide methylation study on essential hypertension in young African American males.

Objective

Method & results

Conclusion

Publications

A genome-wide methylation study on essential hypertension in young African American males.

Similar Datasets

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