Skip to main content
NCBI home page
Chronic Diseases and Translational Medicine logoLink to Chronic Diseases and Translational Medicine
. 2025 May 13;11(3):197–204. doi: 10.1002/cdt3.70008

Epigenetic Changes Related to Hypertension in Asian Adults: A Systematic Review

Lilik Sukesi 1,✉, Yunia Sribudiani 2, Steven Yulius Usman 3, Eric Ricardo Yonatan 3, Ahmedz Widiasta 4, Noormarina Indraswari 5, Ria Bandiara 1, Nanny N M Soetedjo 6
PMCID: PMC12426617  PMID: 40951732

ABSTRACT

Background

Elevated high blood pressure is controlled by complicated, little‐understood genetic and epigenetic pathways that are influenced by both heritable and environmental variables. Many adult systolic and diastolic blood pressure‐related genomic loci have been identified through previous genome‐wide association studies (GWAS); meanwhile, studies specifically on Asian adult populations have not been done. This study aims to comprehensively assess and summarize any gene changes that have been studied and see whether there is a possible influence between epigenetic changes and hypertension in Asian adults.

Methods

This evidence‐based analysis is based on the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 statement and has been registered in PROSPERO under registration number [CRD42024622261]. The data were processed qualitatively to assess the risk of bias using the Newcastle–Ottawa Scale (NOS) and Agency for Health Research and Quality (AHRQ) standards as the threshold. Our study in particular shows that epigenetic modifications may play a role in hypertension, particularly in Asian individuals.

Results

A total of 28 studies were selected for qualitative evaluation. In the adult Asian population, 26 publications (92.8%) reported a relationship between blood pressure and epigenetics. Every study describes a distinct gene or location associated with hypo‐ or hypermethylation. Elevated systolic and diastolic blood pressure was linked to variations of several single‐nucleotide polymorphisms (SNPs), cytosine phosphate guanines (CPGs), and other monogenic genes.

Conclusion

Alterations in epigenetic modifications in potential genes or loci are linked to systolic and diastolic blood pressure of Asian adult populations.

PROSPERO Protocol Registration: CRD42024622261.

Keywords: Asian, blood pressure, DNA methylation, epigenetic, essential hypertension

PRISMA study flow diagram.

graphic file with name CDT3-11-197-g002.jpg

Summary

  • Epigenetic modifications, including hypo‐ and hypermethylation, significantly influence systolic and diastolic blood pressure in Asian adults.

  • Genetic loci variations, including SNPs and CPGs, were strongly linked to hypertension.

  • Provides the first systematic review linking epigenetic modifications to hypertension in Asian adults.

  • Highlights specific genes and loci involved in hypertension, offering potential targets for personalized interventions.

1. Introduction

Elevated blood pressure, commonly referred to as hypertension, is a major modifiable risk factor for ailments related to the kidneys, heart, and brain, such as peripheral vascular disease, heart failure, myocardial infarction, stroke, and coronary artery disease. The American Heart Association/American College of Cardiology has revised the definition of hypertension, which was formerly BP ≥ 140/90 mmHg in adults [1, 2, 3]. Hypertension has become more common, particularly in low‐ and middle‐income nations (LMICs). According to estimates, 1.39 billion persons worldwide—or 31.1% of the total—had hypertension in 2010. Adults with hypertension were more likely to have it in low‐income nations (LMICs; 31.5% of the 1.04 billion population) than in high‐income countries (HICs; 28.5% of the 349 million people) [4, 5, 6]. The reported prevalence of hypertension in East and Southeast Asia varies from 20% in South Korea and Taiwan of China to over 40% in Indonesia, Brunei, and Malaysia [7].

Renal diseases and high blood pressure are controlled by complicated, little‐understood genetic and epigenetic pathways that are influenced by both heritable and environmental variables. High blood pressure and kidney diseases are regulated by complex molecular and pathophysiological systems. These mechanisms show that gene regulation, expression, and function are influenced by genetic determinants and epigenetic factors, which have a significant impact on preconditional settings and susceptibility to the development of hypertension, kidney injury, and dysfunction [8, 9]. Blood pressure and the likelihood of hypertension are also influenced by genetic variations, with a heritability of up to 30%–50%. By itself, the term “epigenetics” describes heritable variations in the patterns of gene expression that are not brought about by modifications to the nucleotide base sequence of DNA and that may be undone by other environmental factors. Important alterations of the epigenetic code include methylation of DNA, RNA‐based mechanisms, and histone changes. Histone acetylases (HATs), histone deacetylases (HDACs), DNA methyl transferases (DNMTs), and histone methyl transferases (HMTs) are four significant epigenetic enzymes that could be the focus of experimental approaches that could result in novel understandings of the identification, treatment, and prevention of hypertension [10, 11].

Single‐nucleotide polymorphisms (SNPs) and monogenic rare variants have been associated for the past 30–40 years by genomic researchers. These associations are primarily caused by mechanisms related to the sympathetic nervous system, NPs (natriuretic peptides), RAAS (renin‐angiotensin aldosterone system), endothelial dysfunction, and inflammation. Changes in the constituents of these pathways may result in genetic and epigenetic disruptions that give rise to hypertension in its early stages [12, 13]. The most recent genome‐wide association studies (GWAS) revealed 2103 independent genetic signals spanning all three BP traits. These signals comprised 267 additional independent significant secondary SNPs from conditional analysis, 113 genome‐wide significant novel loci, and 1723 pairwise‐independent genetic signals among SNPs previously published for BP [14, 15].

Many adult systolic and diastolic blood pressure‐related genomic loci have been identified through previous GWAS. However, relevant studies specifically in Asian adult populations examining the potential impact of epigenetic modifications on the risk of high blood pressure have not been conducted. Therefore, this study aims to comprehensively assess and summarize any gene changes that have been studied previously and see whether there is a possible influence between epigenetic changes and hypertension in Asian adults.

2. Materials and Methods

The study follows the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 to conduct an evidence‐based analysis [16]. The protocol for this review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under registration number [CRD42024622261]. We detailed participants, exposure, comparison, and outcome (PECO); P: Asian Adults respondence with ages over 18 years old (according to Kemenkes RI) with hypertension; E: Epigenetic changes (e.g., DNA Methylation, Histone modification, MicroRNA changes, etc.) on specific gene/locus; C: Asian Adults respondence with ages over 18 years old (according to Kemenkes RI) with no hypertension detected; and O: Hypo/Hypermethylation of DNAs on specific gene or loci are related to hypertension.

Using titles and abstracts, the authors independently located the articles published by December 2024 on PubMed Central, Medline, Springer Link, and ScienceDirect. The references of each study that satisfied the qualifying criteria were manually assessed. (“Epigenetic”) OR (“Genetic Factor”) OR (“Genetic Variant”) OR (“DNA Methylation”) OR (“Histone Modifications”) OR (“RNA Modification”) AND ((“Essential Hypertension”) OR (“Blood Pressure”)) AND (“Asian”) were the bracket keywords we used to combine words. Every study included was found and assessed by investigators on their own. Throughout the literature search, every argument was settled by consensus.

To be included in this systematic review, the study had to fulfill two requirements: (1) it had to be an observational study that looked at the relationship between epigenetic factors and hypertension, such as case‐control, cross‐sectional, and cohort studies; and (2) it had to involve research on Asian Adults. Review articles, editorial remarks, letters, conference abstracts, earlier systematic reviews, meta‐analyses, and investigations involving animals were not included in our selection. We got the full text of possibly eligible studies after screening abstracts and titles for the first study selection to see if they fit our inclusion criteria.

All authors screened titles and abstracts for the initial study selection and obtained the full text of potentially eligible studies to confirm if they met our inclusion criteria. Individually, each researcher collects data from the verified papers and inserts it into an Excel spreadsheet. To reach a final decision, more researchers reconcile any differences. The first author, the research design, the participants, the location, the year of publication, the discussion of a specific locus or gene, and the conclusion on the relationship between epigenetics and childhood‐adolescent hypertension were among the details we gathered from each study. The study's data are all fully disclosed.

The risk of bias in the included studies was evaluated using the Newcastle‐Ottawa Scale [17]. Eight domains were analyzed: nonresponse rate, exposure determination, case representativeness, control selection, control definitions, case–control comparability, and proper case definition. These domains were necessary to conduct case–control and cross‐sectional, non‐randomized control trial or randomized control trial research successfully. The guidelines of the Agency for Health Research and Quality (AHRQ) are employed as a standard to evaluate the caliber of the study [18].

3. Results

3.1. Study Selection and Characteristics

After conducting an extensive search of the literature, we discovered 11,876 articles that may be relevant. Figure 1 displays a flowchart of the included studies. The results showed that, overall, 28 articles met all inclusion criteria [19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46]: 12 were cross‐sectional studies, and 16 were case–control studies. All the specific data are shown in Table S1. However, the heterogeneity across genes or loci that were discussed in every included study made a meta‐analysis impractical.

Figure 1.

Figure 1

Open in a new tab

PRISMA study flow diagram.

Twenty‐eight studies with a total population of 2,140,498 Asian adults over 18 years old were drawn from the majority of Asian populations, namely, China, Indonesia, Korea, and India, as well as research on Asians conducted in England. Out of the 28 studies included in this systematic review, only 2 showed no association between DNA methylation changes and hypertension [28, 33]. This is explained in the study because there is a difference in the potential for genetic changes at a younger age in Asian populations. This may explain, to some extent, the lack of consistency in the observed variable methylation loci. However, this study has limited statistical power due to the relatively small sample size for this analysis.

3.2. DNA Methylation

The majority of research on Asian adults has been found, but researchers have conducted more research using DNA methylation methods to see if there is a genetic relationship to hypertension. The four dominant genes shown to influence hypertension in Asian adults are RAAS‐related genes, inflammatory cytokine‐related genes, homocysteine‐related genes, and BMI‐related genes. RAAS‐related genes, such as α‐adducin1 (ADD1) [19, 38], Aldosterone synthase (CYP11B2), Glucokinase (GCK) [21], Angiotensin II Type 1 Receptor (AGTR1) [23, 26, 30, 35], are reported in this systematic review. Hypomethylation of these genes has been shown to be a significant predictor of essential hypertension in Asian Adults.

Inflammatory‐related genes, such as Hypomethylation of interleukin‐6 (IL‐6) of cytosine‐phosphate–guanine (CpG) II–III and interferon‐gamma (IFN‐γ), are shown to be a risk factor for EH [27, 28, 29]. Hypermethylation of homocysteine (hcy)‐related hypertension genes, such as methylenetetrahydrofolate dehydrogenase 1 (MTHFD1), is reported as a possible biomarker for the identification of essential hypertension [32]. Lipid pathway and BMI‐related genes such as ATP‐binding cassette transporter G1 (ABCG1), Polypeptide N‐Acetylgalactosaminyltransferase 2 (GALNT2) [20, 46] lncRNA p53 regulated, and ESC associated 1 (LNCPRESS1), Oxoglutarate Dehydrogenase L (OGDHL), RNA, U1 small nuclear 44, pseudogene (RNU1‐44P), Nephrin (NPHS1), endothelin converting enzyme‐like 1 pseudogene 2 (ECEL1P2), Lethal Giant Larvae 2 (LLGL2), Y RNA 4 pseudogene 15 (RNY4P15), Monoacylglycerol O‐Acyltransferase 3 (MOGAT3), Phosphatase And Actin Regulator 3 (PHACTR3), and Brain‐specific angiogenesis inhibitor 2 (BAI2) are significantly associated with an elevated risk of coronary heart disease and hypertension; meanwhile, HMG‐CoA reductase (HMGCR) are not associated considerably.

Other genes like, vascular smooth muscle‐related genes such as Insulin‐like growth factor‐binding protein 3 (IGFBP3), Potassium Two Pore Domain Channel Subfamily K Member 3 (KCNK3), Phosphodiesterase 3 A (PDE3A) and PR/SET Domain 6 (PRDM6), also renal related genes, such as Rho GTPase Activating Protein 24 (ARHGAP24), Protein odd‐skipped‐related 1 (OSR1), Solute Carrier Family 22 Member 7 (SLC22A7), T‐Box Transcription Factor 2 (TBX2), mitochondrial function related genes (mitofusin 2 gene [Mfn2]), Growth factor related genes, such as type V collage (COL5A1), Phospholipase C Eta 2 (PLCH2), and Wnt Family Member 3A (WNT3A), mitochondrial function related genes (MT‐COX3), atrial natriuretic peptide cardiac hormone related genes (Serine Peptidase [CORIN]), Endothelin‐converting enzyme (ECE‐1) gene, and endothelial nitric oxide synthase (eNOS) gene are reported to be correlated with hypertension in Asian Adults [22, 31, 41, 42, 43, 44]. Hypomethylation of non‐voltage‐gated 1 alpha subunit (SCNN1A), an epithelial sodium‐channel related gene, is also related to hypertension [24]. Meanwhile, noradrenergic neuron‐related genes like norepinephrine (NET) have shown no correlation between depression and hypertension and the DNA methylation levels of nine CpG sites in the promoter region of the NET gene [28].

3.3. RNA Modification and Histone Modification

There are still few studies with Asian adult populations using histone and RNA modification approaches in their research. From the many studies that have been conducted, only 3 studies were found to meet our inclusion criteria. Histone H3 acetyl Lys9 (H3K9ac), methylated histone H3 Lys9 (H3K9me3), methylated histone H3 Lys27 (H3K27me3), and methylated histone H3 Lys36 (H3K36me3) are shown to have negative correlations with certain prework blood pressure metrics. SBP, DBP, and MAP gene [25], and microRNA 21,29, and 199 (miR‐21, miR‐29, and miR‐199) are associated with H‐type hypertension and may serve as biomarkers to provide clues to the potential pathogenesis of H‐type hypertension. Hypomethylation of miR‐21 was shown to be correlated with hcy, and hypermethylation of miR‐199 was positively correlated with hcy, which influenced hypertension [37].

3.4. Risk of Bias

From a total of 28 studies that were included in qualitative synthesis, 26 of the studies have good quality, based on utilizing Newcastle‐Ottawa Scale [NOS] and Agency for Health Research and Quality (AHRQ), except studies by Bao et al. [29] and Fan et al. [21] having fair quality, because the study only reaches two out of four requirements in the selection domain, specifically due to the lack of details regarding the selection and definition of control subjects on Fan et al., and the process of the selection population by Bao et al. study. The overall results of the study quality assessment in the form of a visual star of every domain are shown in Figure 2.

Figure 2.

Figure 2

Open in a new tab

Risk of bias in included case‐control and cross‐sectional studies was assessed using the Newcastle‐Ottawa Scale and the Agency for Health Research and Quality (AHRQ) guidelines.

4. Discussion

Currently, as we are aware, this is the first systematic review that thoroughly examines the adult Asian population. Our study showed that 23 publications (92%) have a significant relationship between blood pressure and epigenetics. We found a connection between high levels of DBP and SBP and extensive hypo‐ or hypermethylation. Our research suggests that DNA methylation, in particular, may be a key factor in the control of BP's molecular mechanisms.

In this study, ADD1 [19, 38], GCK [21], CYP11B2 [38], and AGTR [23, 26, 30, 35] are mentioned as being related to hypertension. These are in line with the previous theory and studies related to RAAS. Adducin (ADD1) is a promising candidate gene for essential hypertension, as it is one of the angiotensin subcomponents in RAAS, due to its ability to enhance renal salt reabsorption and its direct involvement in the pathogenesis of essential hypertension [47, 48]. Previous old meta‐analysis data [49] and a study by Wang et al. [50] stated that ADD1 is related to essential hypertension, mostly with low‐density lipoprotein levels. According to Wang et al., the prevalence of α‐adducin gene 614 T in normotensives and hypertensives in South China was 42.53%–58.24% [50]. Moreover, a previous study stated that the frequency of the α‐adducin gene 614 T allele was 46%–48% in Chinese, 59%–61% in Koreans, 54%–60% in Japanese, and 33%–53% in Americans [51]. Though it proved higher in Asian adult populations, further research with a larger sample size is needed to prove the relationship.

Angiotensin II is also a key peptide effector in RAAS that causes water‐sodium retention and vasoconstriction. The genes for angiotensin II receptor type 1 (AGTR1) and type 2 (AGTR2) are subtypes of AGTR, and research has shown a strong correlation between the AGTR1 gene and the development of hypertension and other cardiac consequences [52]. Same with GCK, GCK is proven to be related as a key enzyme involved in glucose metabolism. Numerous investigations have already revealed the connection between GCK polymorphisms and EH. There is a strong correlation between GCK gene‐body hypomethylation and the risk of coronary heart disease, which is linked to EH [53, 54]. Those studies [19, 21, 23, 26, 30, 35, 37] are also in line with the previous study by Holmes et al. [55], which stated that hypertension was linked to the hypomethylation of ADD1 GCK and AGTR1 (CES = 2.3%, 95% CI, −2.51 to 7.07).

The clinical and physiological significance of chronic low‐grade inflammation in EH and cardiovascular illnesses has been recognized [56]. Some studies included in this systematic review [27, 29] discussed the possibility of pro‐inflammatory genes related to EH, and it proved to be in line with previous cross‐sectional studies that stated tumor necrosis factor‐α, IL‐6, C‐reactive protein, and EH were linked, which included an ethnic investigation of atherosclerosis [57]. On the other hand, IFN‐γ may attach to vascular smooth muscle cells in vitro to control blood pressure, impact vascular endothelial cells, and perform immune regulatory, anticancer, and antibacterial actions. It is proven from the theory that reduced DNA methylation in vascular tissues increases the vulnerability to mutations or aberrant gene expression patterns by promoting the deposition of lipids and vascular smooth cells, which transforms the phenotype from normal to vascular fibrotic lesions [58, 59]. However, it is still unclear what biological pathway leads to elevated levels of inflammatory cytokines.

Other genes, such as MTHFD1, are also reported to be related to hypertension. This is also in line with the previous theory that stated evidence of hypermethylation of the MTHFD1 gene was found in cases of essential hypertension, which resulted in the MTHFD1 gene being silenced, and a buildup of Hcy levels would increase the risk of developing critical hypertension [32, 60]. Two studies stated no correlation between epigenetic changes and hypertension [25, 28]. H3K9me3‐specific demethylase JMJD2A/KDM4A, theoretically in particular, is upregulated in hypertrophic cardiomyopathy, a condition that causes increased ventricular thickness and is frequently linked to raised blood pressure. Consequently, dysregulation of JMJD2A/KDM4A may lead to a reduction in H3K9me3 concentrations, an increase in the risk of hypertrophic cardiomyopathy, and an increase in blood pressure [61]. Despite the limited data, these studies collectively explain the histone study's observed inverse relationship between H3K9me3 regulation and blood pressure indicators [25]. Nevertheless, theoretically, norepinephrine transporter (NET) are related to neural‐sodium symporter (NSS) transporters, including those for dopamine (DAT) and serotonin (SERT), which influence blood pressure in the human body by increasing heart rate, cardiac contractility, vascular tone, renin‐angiotensin system activity, and renal sodium reabsorption [62]. According to a recent study, the decrease in NET expression was linked to the enrichment of MeCP2 and H3K9 trimethylation in the NET promoter region [63, 64]. These data revealed that the MeCP2 corepressor and histone modifications may be the main epigenetic regulatory mechanisms governing NET silencing; however, earlier research evaluated NETs based on DNA methylation rather than utilizing histone alterations. The outcome of DNA methylation assays is thus negative.

This study has several limitations because very few studies have been conducted specifically on the histone and RNA modifications to compare the possibility of hypertension caused by epigenetic changes. The range of genes or SNP loci hypothesized to be linked to hypertension limits this investigation since few studies have used the same genes so that findings can be compared between treatments. It is also challenging to conclude temporal relationships because most of the included research seems to be cross‐sectional. There is also methodological heterogeneity across all genes of the included studies, which makes a meta‐analysis unfeasible.

5. Conclusion

This study provides a theoretical foundation for future research on the association between epigenetic modifications in candidate genes/loci and blood pressure in Asian adults. Future studies should include larger, more diverse populations and adopt longitudinal designs to confirm better and clarify the relationship between specific genes and hypertension.

Author Contributions

Lilik Sukesi and Yunia Sribudiani: conceptualization, methodology, formal – analysis, investigation, resources writing – original draft, writing – review and editing, visualization, and supervisor project administration. Steven Yulius Usman and Eric Ricardo Yonatan: data curation, methodology, software validation, formal – analysis, investigation, resources writing – original draft, writing – review and editing. Ahmedz Widiasta: data curation, methodology, formal – analysis, investigation, resources writing – original draft, writing – review and editing, visualization, and supervisor project administration. Noormarina Indraswari: data curation, methodology, software validation, formal – analysis, investigation, resources writing – original draft, writing – review and editing, visualization. Ria Bandiara and Nanny N. M. Soetedjo: conceptualization, resources writing – original draft, writing – review and editing, visualization, supervisor project administration.

Ethics Statement

This systematic review has been registered in PROSPERO under registration number [CRD42024622261].

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

supplementary Table.

CDT3-11-197-s001.docx (53.8KB, docx)

Acknowledgments

The authors have nothing to report.

Data Availability Statement

The authors confirm that the data and materials supporting the findings of this study are available in the article.

References

  • 1. Benjamin E. J., Muntner P., Alonso A., et al., “Heart Disease and Stroke statistics—2019 Update: A Report From the American Heart Association,” Circulation 139, no. 10 (2019): e67–e69, 10.1161/CIR.0000000000000659. [DOI] [PubMed] [Google Scholar]
  • 2. Whelton P. K., Carey R. M., Aronow W. S., et al., “2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APHA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines,” Hypertension (Dallas, TX: 1979) 71, no. 6 (2018): 1269–1324, 10.1161/HYP.0000000000000066. [DOI] [PubMed] [Google Scholar]
  • 3. Mozaffarian D., “Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity: A Comprehensive Review,” Circulation 133, no. 2 (2016): 187–225, 10.1161/CIRCULATIONAHA.115.018585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. Mills K. T., Stefanescu A., and He J., “The Global Epidemiology of Hypertension,” Nature Reviews Nephrology 16, no. 4 (2020): 223–237, 10.1038/s41581-019-0244-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5. Mills K. T., Bundy J. D., Kelly T. N., et al., “Global Disparities of Hypertension Prevalence and Control: A Systematic Analysis of Population‐Based Studies From 90 Countries,” Circulation 134, no. 6 (2016): 441–450, 10.1161/CIRCULATIONAHA.115.018912. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Roth G. A., Abate D., Abate K. H., et al., “Global, Regional, and National Age‐Sex‐Specific Mortality for 282 Causes of Death in 195 Countries and Territories, 1980–2017: A Systematic Analysis for the Global Burden of Disease Study 2017,” Lancet 392, no. 10159 (2018): 1736–1788, 10.1016/S0140-6736(18)32203-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7. Zhou B., Carrillo‐Larco R. M., Danaei G., et al., “Worldwide Trends in Hypertension Prevalence and Progress in Treatment and Control From 1990 to 2019: A Pooled Analysis of 1201 Population‐Representative Studies With 104 Million Participants,” Lancet 398, no. 10304 (2021): 957–980, 10.1016/S0140-6736(21)01330-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8. Hoffmann T. J., Ehret G. B., Nandakumar P., et al., “Genome‐Wide Association Analyses Using Electronic Health Records Identify New Loci Influencing Blood Pressure Variation,” Nature Genetics 49, no. 1 (2017): 54–64, 10.1038/ng.3715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9. Shi Y., Zhang H., Huang S., et al., “Epigenetic Regulation in Cardiovascular Disease: Mechanisms and Advances in Clinical Trials,” Signal Transduction and Targeted Therapy 7, no. 1 (2022): 200, 10.1038/s41392-022-01055-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10. Pandey K. N., “Genetic and Epigenetic Mechanisms Regulating Blood Pressure and Kidney Dysfunction,” Hypertension 81, no. 7 (2024): 1424–1437, 10.1161/HYPERTENSIONAHA.124.22072. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11. Pratamawati T. M., Alwi I., and Asmarinah. “Summary of Known Genetic and Epigenetic Modification Contributed to Hypertension.” International Journal of Hypertension 2023 (2023): 5872362. 10.1155/2023/5872362. [DOI] [PMC free article] [PubMed]
  • 12. Padmanabhan S. and Dominiczak A. F., “Genomics of Hypertension: The Road to Precision Medicine,” Nature Reviews Cardiology 18, no. 4 (2021): 235–250, 10.1038/s41569-020-00466-4. [DOI] [PubMed] [Google Scholar]
  • 13. Ettehad D., Emdin C. A., Kiran A., et al., “Blood Pressure Lowering for Prevention of Cardiovascular Disease and Death: A Systematic Review and Meta‐Analysis,” Lancet 387, no. 10022 (2016): 957–967, 10.1016/S0140-6736(15)01225-8. [DOI] [PubMed] [Google Scholar]
  • 14. Evangelou E., Warren H. R., Mosen‐Ansorena D., et al., “Genetic Analysis of Over 1 Million People Identifies 535 New Loci Associated With Blood Pressure Traits,” Nature Genetics 50, no. 10 (2018): 1412–1425, 10.1038/s41588-018-0205-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Keaton J. M., Kamali Z., Xie T., et al., “Genome‐Wide Analysis in Over 1 Million Individuals of European Ancestry Yields Improved Polygenic Risk Scores for Blood Pressure Traits,” Nature Genetics 56, no. 5 (2024): 778–791, 10.1038/s41588-024-01714-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16. Page M. J., McKenzie J. E., Bossuyt P. M., et al., “The PRISMA 2020 Statement: An Updated Guideline for Reporting Systematic Reviews,” BMJ 372 (2021): n71, 10.1136/bmj.n71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17. Wells G. A., Shea B., O'Connell D., et al., The Newcastle‐Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta‐analyses (Department of Epidemiology and Community Medicine, University of Ottawa; ), http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. [Google Scholar]
  • 18. Kronick R., “AHRQ's Role in Improving Quality, Safety, and Health System Performance,” Public Health Reports® 131, no. 2 (2016): 229–232, 10.1177/003335491613100205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Zhang L. N., Liu P. P., Wang L., et al., “Lower ADD1 Gene Promoter DNA Methylation Increases the Risk of Essential Hypertension,” PLoS One 8, no. 5 (2013): e63455, 10.1371/journal.pone.0063455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Peng P., Wang L., Yang X., et al., “A Preliminary Study of the Relationship Between Promoter Methylation of the ABCG1, GALNT2 and HMGCR Genes and Coronary Heart Disease,” PLoS One 9, no. 8 (2014): e102265, 10.1371/journal.pone.0102265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Fan R., Wang W. J., Zhong Q. L., et al., “Aberrant Methylation of the GCK Gene Body Is Associated With the Risk of Essential Hypertension,” Molecular Medicine Reports 12, no. 2 (2015): 2390–2394, 10.3892/mmr.2015.3631. [DOI] [PubMed] [Google Scholar]
  • 22. Kato N., Loh M., Takeuchi F., et al., “Trans‐Ancestry Genome‐Wide Association Study Identifies 12 Genetic Loci Influencing Blood Pressure and Implicates a Role for DNA Methylation,” Nature Genetics 47, no. 11 (2015): 1282–1293, 10.1038/ng.3405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Fan R., Mao S., Zhong F., et al., “Association of AGTR1 Promoter Methylation Levels With Essential Hypertension Risk: A Matched Case‐Control Study,” Cytogenetic and Genome Research 147, no. 2–3 (2015): 95–102, 10.1159/000442366. [DOI] [PubMed] [Google Scholar]
  • 24. Mao S., Fan R., Gu T., et al., “Hypermethylation of SCNN1A Gene‐Body Increases the Risk of Essential Hypertension,” International Journal of Clinical and Experimental Pathology 9 (2016): 8047–8056. [Google Scholar]
  • 25. Kresovich J. K., Zhang Z., Fang F., et al., “Histone 3 Modifications and Blood Pressure in the Beijing Truck Driver Air Pollution Study,” Biomarkers 22, no. 6 (2017): 584–593, 10.1080/1354750X.2017.1347961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. Lin J., Lin S., Wu Y., Wang X., Wu S., and Li H., “Hypomethylation of the Angiotensin II Type I Receptor (AGTR1) Gene Along With Environmental Factors Increases the Risk for Essential Hypertension,” Cardiology 137, no. 2 (2017): 126–135, 10.1159/000458520. [DOI] [PubMed] [Google Scholar]
  • 27. Mao S., Sun J., Gu T., Zhu F., Yin F., and Zhang L., “Hypomethylation of Interleukin‐6 (IL‐6) Gene Increases the Risk of Essential Hypertension: A Matched Case‐Control Study,” Journal of Human Hypertension 31, no. 8 (2017): 530–536, 10.1038/jhh.2017.7. [DOI] [PubMed] [Google Scholar]
  • 28. Meng L., Chen D., Pei F., Hui R., Zheng Y., and Chen J., “DNA Methylation in the Norepinephrine Transporter Gene Promoter Region Is Not Associated With Depression and Hypertension,” Clinical and Experimental Hypertension 39, no. 6 (2017): 539–545, 10.1080/10641963.2017.1288737. [DOI] [PubMed] [Google Scholar]
  • 29. Bao X. J., Mao S. Q., Gu T. L., Zheng S. Y., Zhao J. S., and Zhang L. N., “Hypomethylation of the Interferon γ Gene as a Potential Risk Factor for Essential Hypertension: A Case‐Control Study,” Tohoku Journal of Experimental Medicine 244, no. 4 (2018): 283–290, 10.1620/tjem.244.283. [DOI] [PubMed] [Google Scholar]
  • 30. Wulandari A., Widodo M., Sardjono T., and Lyrawati D., “Angiotensinogen II Type I Receptor A1166C Is Associated With Serum Sodium Level and Essential Hypertension in Javanese Population,” Indian Journal of Public Health Research & Development 9 (2018): 415, 10.5958/0976-5506.2018.01872.7. [DOI] [Google Scholar]
  • 31. Jin F., Li X., Wang Z., et al., “Association of Mitofusin 2 Methylation and Essential Hypertension: A Case‐Control Study in a Chinese Population,” Hypertension Research 41, no. 8 (2018): 605–613, 10.1038/s41440-018-0057-x. [DOI] [PubMed] [Google Scholar]
  • 32. Xu M., Li J., Chen X., Han L., Li L., and Liu Y., “MTHFD1 Promoter Hypermethylation Increases the Risk of Hypertension,” Clinical and Experimental Hypertension 41, no. 5 (2019): 422–427, 10.1080/10641963.2018.1501057. [DOI] [PubMed] [Google Scholar]
  • 33. Kazmi N., Elliott H. R., Burrows K., et al., “Associations Between High Blood Pressure and DNA Methylation,” PLoS One 15, no. 1 (2020): e0227728. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34. Gao Y., Pang H., Chen B., et al., “Genome‐Wide Analysis of DNA Methylation and Risk of Cardiovascular Disease in a Chinese Population,” BMC Cardiovascular Disorders 21, no. 1 (2021): 240, 10.1186/s12872-021-02001-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35. Li Z., Ma Q., Li X., et al., “Association of AGTR1 Gene Methylation and Its Genetic Variant in Chinese Farmer With Hypertension: A Case‐Control Study,” Medicine 101, no. 29 (2022): e29712, https://journals.lww.com/md-journal/fulltext/2022/07220/association_of_agtr1_gene_methylation_and_its.12.aspx. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36. Nguyen T. M., Le H. L., Hwang K. B., Hong Y. C., and Kim J. H., “Predicting High Blood Pressure Using DNA Methylome‐Based Machine Learning Models,” Biomedicines 10, no. 6 (2022): 1406, 10.3390/biomedicines10061406. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. He X., Ma R., Li Y., et al., “Association of H‐Type Hypertension With miR‐21, miR‐29, and miR‐199 in Kazakhs of Xinjiang, China,” International Journal of Hypertension (2022): 4632087, 10.1155/2022/4632087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Zhang Y., Chang P., and Liu Z., “ADD1 Single Nucleotide Polymorphisms Are Associated With Essential Hypertension Among Han and Mongolian Population in Inner Mongolia Area,” Frontiers in Genetics 13 (2022): 931803, 10.3389/fgene.2022.931803. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39. Zhang H., Wang A., Xu T., Mo X., and Zhang Y., “Promoter DNA Methylation in GWAS‐Identified Genes as Potential Functional Elements for Blood Pressure: An Observational and Mendelian Randomization Study,” Frontiers in Genetics 12 (2022): 791146, 10.3389/fgene.2021.791146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40. Hong X., Miao K., Cao W., et al., “Association Between DNA Methylation and Blood Pressure: A 5‐Year Longitudinal Twin Study,” Hypertension 80, no. 1 (2023): 169–181, 10.1161/HYPERTENSIONAHA.122.19953. [DOI] [PubMed] [Google Scholar]
  • 41. Wang W., Yao J., Li W., et al., “Epigenome‐Wide Association Study in Chinese Monozygotic Twins Identifies DNA Methylation Loci Associated With Blood Pressure,” Clinical Epigenetics 15, no. 1 (2023): 38, 10.1186/s13148-023-01457-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42. Zhao L., Jia Y. N., Liu Q., et al., “Association Between Mitochondrial DNA Methylation and Hypertension Risk: A Cross‐Sectional Study in Chinese Northern Population,” Biomedical and Environmental Sciences: BES 36, no. 10 (2023): 972–978, 10.3967/bes2023.122. [DOI] [PubMed] [Google Scholar]
  • 43. Shi J., Wu L., Chen Y., et al., “Association Between CORIN Methylation and Hypertension in Chinese Adults,” Postgraduate Medical Journal 99, no. 1173 (July 2023): 753–762, 10.1136/pmj-2022-141802. [DOI] [PubMed] [Google Scholar]
  • 44. Jiang H., Yang X., You S., Liu T., and Zhang S. L., “DNA Methylation Profile of Essential Hypertension in a Xinjiang Kazak Population in China,” Preprint 1 (2023): 1–18, 10.21203/rs.3.rs-3743285/v1. [DOI] [Google Scholar]
  • 45. Kaushik A., Bhattacharjee D., Chaudhary V., et al., “Hypertension and Global DNA Methylation: A Population‐Based Study in Rural, Punjab, India,” Scientific Reports 14 (2024): 25826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. Yao J., Ning F., Wang W., and Zhang D., “DNA Methylation Mediated the Association of Body Mass Index With Blood Pressure in Chinese Monozygotic Twins,” Twin Research and Human Genetics 27, no. 1 (2024): 18–29, 10.1017/thg.2024.3. [DOI] [PubMed] [Google Scholar]
  • 47. Gupta S., Jhawat V., Agarwal B. K., Roy P., and Saini V., “Alpha Adducin (ADD1) Gene Polymorphism and New Onset of Diabetes Under the Influence of Selective Antihypertensive Therapy in Essential Hypertension,” Current Hypertension Reviews 15, no. 2 (2019): 123–134, 10.2174/1573402114666180731111453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48. Adithan C., Ramu P., Umamaheswaran G., Shewade D., Swaminathan R., and Balachander J., “Gly460Trp Polymorphism of the ADD1 Gene and Essential Hypertension in an Indian Population: A Meta‐Analysis on Hypertension Risk,” Indian Journal of Human Genetics 16, no. 1 (2010): 8, 10.4103/0971-6866.64938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49. Lei Y., “Association of Alpha‐ADD1 Gene and Hypertension Risk: A Meta‐Analysis,” Medical Science Monitor 21 (2015): 1634–1641, 10.12659/MSM.893191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50. Wang L., Zheng B., Zhao H., et al., “α‐Adducin Gene G614T Polymorphisms in Essential Hypertension Patients With High Low‐Density Lipoprotein (LDL) Levels,” Indian Journal of Medical Research 0139 (2014): 273–278. [PMC free article] [PubMed] [Google Scholar]
  • 51. He X., Zhu D. L., Chu S. L., et al., “α‐Adducin Gene and Essential Hypertension in China,” Clinical and Experimental Hypertension 23, no. 7 (2001): 579–589, 10.1081/ceh-100106828. [DOI] [PubMed] [Google Scholar]
  • 52. Forrester S. J., Booz G. W., Sigmund C. D., et al., “Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology,” Physiological Reviews 98, no. 3 (2018): 1627–1738, 10.1152/physrev.00038.2017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53. Xu L., Zheng D., Wang L., et al., “GCK Gene‐Body Hypomethylation Is Associated With the Risk of Coronary Heart Disease,” BioMed Research International 2014 (2014): 151723, 10.1155/2014/151723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54. Nadeem M., Ahmed S. S., Mansoor S., and Farooq S., “Risk Factors for Coronary Heart Disease in Patients Below 45 Years of Age,” Pakistan Journal of Medical Sciences 29, no. 1 (2012): 91–96, 10.12669/pjms.291.2828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55. Holmes L., Lim A., Comeaux C. R., Dabney K. W., and Okundaye O., “DNA Methylation of Candidate Genes (ACE II, IFN‐γ, AGTR 1, CKG, ADD1, SCNN1B, and TLR2) in Essential Hypertension: A Systematic Review and Quantitative Evidence Synthesis,” International Journal of Environmental Research and Public Health 16, no. 23 (2019): 4829, 10.3390/ijerph16234829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56. Gusev E. and Sarapultsev A., “Atherosclerosis and Inflammation: Insights From the Theory of General Pathological Processes,” International Journal of Molecular Sciences 24, no. 9 (2023): 7910, 10.3390/ijms24097910. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57. Bautista L. E., Vera L. M., Arenas I. A., and Gamarra G., “Independent Association Between Inflammatory Markers (C‐Reactive Protein, Interleukin‐6, and TNF‐α) and Essential Hypertension,” Journal of Human Hypertension 19, no. 2 (2005): 149–154, 10.1038/sj.jhh.1001785. [DOI] [PubMed] [Google Scholar]
  • 58. Lin C. F., Lin C. M., Lee K. Y., et al., “Escape From IFN‐γ‐Dependent Immunosurveillance in Tumorigenesis,” Journal of Biomedical Science 24, no. 1 (2017): 10, 10.1186/s12929-017-0317-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59. Kawano H., Saeki H., Kitao H., et al., “Chromosomal Instability Associated With Global DNA Hypomethylation Is Associated With the Initiation and Progression of Esophageal Squamous Cell Carcinoma,” Annals of Surgical Oncology 21, no. Suppl 4 (2014): 696–702, 10.1245/s10434-014-3818-z. [DOI] [PubMed] [Google Scholar]
  • 60. Field M. S., Kamynina E., and Stover P. J., “MTHFD1 Regulates Nuclear De Novo Thymidylate Biosynthesis and Genome Stability,” Biochimie 126 (2016): 27–30, 10.1016/j.biochi.2016.02.001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61. Zhu Q., Liang F., Cai S., et al., “KDM4A Regulates Myogenesis by Demethylating H3K9me3 of Myogenic Regulatory Factors,” Cell Death & Disease 12, no. 6 (2021): 514, 10.1038/s41419-021-03799-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62. Schroeder C. and Jordan J., “Norepinephrine Transporter Function and Human Cardiovascular Disease,” American Journal of Physiology‐Heart and Circulatory Physiology 303, no. 11 (2012): H1273–H1282, 10.1152/ajpheart.00492.2012. [DOI] [PubMed] [Google Scholar]
  • 63. Bayles R., Kn H., Lambert E., et al., “Epigenetic Modification of the Norepinephrine Transporter Gene in Postural Tachycardia Syndrome,” Arteriosclerosis, Thrombosis, and Vascular Biology 32, no. 8 (2012): 1910–1916, 10.1161/ATVBAHA.111.244343. [DOI] [PubMed] [Google Scholar]
  • 64. Kn H., Bayles R., Ciccotosto G. D., et al., “Alleviating Transcriptional Inhibition of the Norepinephrine Slc6a2 Transporter Gene in Depolarized Neurons,” Journal of Neuroscience 30, no. 4 (2010): 1494–1501, 10.1523/JNEUROSCI.4675-09.2010. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

supplementary Table.

CDT3-11-197-s001.docx (53.8KB, docx)

Data Availability Statement

The authors confirm that the data and materials supporting the findings of this study are available in the article.

Articles from Chronic Diseases and Translational Medicine are provided here courtesy of Chinese Medical Association

RESOURCES