Associations between high blood pressure and DNA methylation

Kazmi, Nabila; Elliott, Hannah R; Burrows, Kimberley; Tillin, Therese; Hughes, Alun D.; Chaturvedi, Nishi; Gaunt, Tom R.; Relton, Caroline L

doi:10.1371/journal.pone.0227728

Cited by 45 publications

(35 citation statements)

References 53 publications

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“…No CpG sites were associated with hypertension in EWASdb. Similarly, no evidence of associations between DNA methylation and hypertension was found in another recent study [ 39 ].…”

Section: Methodsmentioning

confidence: 78%

See 1 more Smart Citation

Cell lineage-specific methylome and genome alterations in gout

Tseng

Liao

Wong

et al. 2021

Aging

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In this study, we examined data from 69 gout patients and 1,455 non-gout controls using a MethylationEPIC BeadChip assay and Illumina HiSeq platform to identify lineage-specific epigenetic alterations and associated genetic factors that contributed to gouty inflammation. Cell lineage-specific differentially methylated sites were identified using CellDMC after adjusting for sex, age, alcohol drinking, smoking status, and smoking history (total pack-years). Different cell lineages displayed distinct differential methylation. Ingenuity Pathway Analysis and NetworkAnalyst indicated that many differential methylated sites were associated with interleukin-1β expression in monocytes. On the UCSC Genome Browser and WashU Epigenome Browser, metabolic trait, cis-methylation quantitative trait loci, genetic, and functional annotation analyses identified nine methylation loci located in interleukin-1β-regulating genes ( PRKCZ, CIDEC, VDAC1, CPT1A, BIRC2, BRCA1, STK11, and NLRP12 ) that were associated specifically with gouty inflammation. All nine sites mapped to active regulatory elements in monocytes. MoLoTool and ReMap analyses indicated that the nine methylation loci overlapped with binding sites of several transcription factors that regulated interleukin-1β production and gouty inflammation. Decreases in PRKCZ and STK11 methylation were also associated with higher numbers of first-degree relatives who also had gout. The gouty-inflammation specific methylome and genome alterations could potentially aid in the identification of novel therapeutic targets.

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“…No CpG sites were associated with hypertension in EWASdb. Similarly, no evidence of associations between DNA methylation and hypertension was found in another recent study [ 39 ].…”

Section: Methodsmentioning

confidence: 78%

“…None of these final nine CpG sites were associated with body mass index ( Supplementary Table 6 ) according to EWASdb. A separate study also found no associations between DNA methylation and hypertension [ 39 ].…”

Section: Resultsmentioning

confidence: 99%

Cell lineage-specific methylome and genome alterations in gout

Tseng

Liao

Wong

et al. 2021

Aging

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“…The other study of incident T2DM reported additional loci such as PHGDH and CPT1A , which were discovered among Europeans and replicated among Indian Asians 80 . The study of blood pressure compared the methylation profiles between Europeans and South Asians revealed many distinct loci between the two ancestries with a small overlap 84 . To our current knowledge, some known trans-ethic epigenetic loci might be transportable from Europeans to South Asians, but there is still a lack in studies specifically among large South Asian populations to further explore novel loci to explain the higher risk.…”

Section: Epigenetic Signatures Identify Molecular Pathways Of Cvd That Are Activated In the Context Of Environmental Riskmentioning

confidence: 99%

Cardiovascular disease risk and pathophysiology in South Asians: can longitudinal multi-omics shed light?

et al. 2021

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Cardiovascular disease (CVD) is the leading cause of mortality in South Asia, with rapidly increasing prevalence of hypertension, type 2 diabetes (T2DM) and hyperlipidemia over the last two decades. Atherosclerotic CVD (ASCVD) affects South Asians earlier in life and at lower body weights, which is not fully explained by differential burden of conventional risk factors. Heart failure (HF) is a complex clinical syndrome of heterogeneous structural phenotypes including two major clinical subtypes, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF). The prevalence of HF in South Asians is also rising with other metabolic diseases, and HFpEF develops at younger age and leaner body mass index in South Asians than in Whites. Recent genome-wide association studies, epigenome-wide association studies and metabolomic studies of ASCVD and HF have identified genes, metabolites and pathways associated with CVD traits. However, these findings were mostly driven by samples of European ancestry, which may not accurately represent the CVD risk at the molecular level, and the unique risk profile of CVD in South Asians. Such bias, while formulating hypothesis-driven research studies, risks missing important causal or predictive factors unique to South Asians. Importantly, a longitudinal design of multi-omic markers can capture the life-course risk and natural history related to CVD, and partially disentangle putative causal relationship between risk factors, multi-omic markers and subclinical and clinical ASCVD and HF. In conclusion, combining high-resolution untargeted metabolomics with epigenomics of rigorous, longitudinal design will provide comprehensive unbiased molecular characterization of subclinical and clinical CVD among South Asians. A thorough understanding of CVD-associated metabolomic profiles, together with advances in epigenomics and genomics, will lead to more accurate estimates of CVD progression and stimulate new strategies for improving cardiovascular health.

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“…Inflammatory factors are known to upregulate the expression of LOXL2 and thereby increase fibrosis [ 105 ]. In addition, an epigenome-wide association study conducted on Asian and European cohorts showed that genes that are known to have an association with hypertension were differentially methylated, and that there were differences between the methylation statuses of the two cohorts [ 106 ]. It was also shown in a mouse model that if DNMT1, an enzyme that catalyzes methylation, is silenced, an upregulation is seen in the interleukins and cytokines, thus increasing inflammation [ 107 ].…”

Section: Epigenetic Control Of Loxl2 Expressionmentioning

confidence: 99%

Linking LOXL2 to Cardiac Interstitial Fibrosis

Erasmus

Samodien

Lecour

et al. 2020

IJMS

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Cardiovascular diseases (CVDs) are the leading causes of death worldwide. CVD pathophysiology is often characterized by increased stiffening of the heart muscle due to fibrosis, thus resulting in diminished cardiac function. Fibrosis can be caused by increased oxidative stress and inflammation, which is strongly linked to lifestyle and environmental factors such as diet, smoking, hyperglycemia, and hypertension. These factors can affect gene expression through epigenetic modifications. Lysyl oxidase like 2 (LOXL2) is responsible for collagen and elastin cross-linking in the heart, and its dysregulation has been pathologically associated with increased fibrosis. Additionally, studies have shown that, LOXL2 expression can be regulated by DNA methylation and histone modification. However, there is a paucity of data on LOXL2 regulation and its role in CVD. As such, this review aims to gain insight into the mechanisms by which LOXL2 is regulated in physiological conditions, as well as determine the downstream effectors responsible for CVD development.

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Associations between high blood pressure and DNA methylation

Cited by 45 publications

References 53 publications

Cell lineage-specific methylome and genome alterations in gout

Cell lineage-specific methylome and genome alterations in gout

Cardiovascular disease risk and pathophysiology in South Asians: can longitudinal multi-omics shed light?

Linking LOXL2 to Cardiac Interstitial Fibrosis

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