Hypomethylation of interleukin-6 (IL-6) gene increases the risk of essential hypertension: a matched case–control study

Mao, Shuqi; Jh, Sun; Tl, Gu; Fb, Zhu; Fy, Yin; Ln, Zhang

doi:10.1038/jhh.2017.7

Cited by 32 publications

(24 citation statements)

References 39 publications

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“…Increasing the methylation level of a promoter region will silence the transcription of the corresponding gene, whereas decreasing it may promote gene transcription . Aberrant gene methylation has been identified as an important contributor to the pathogenesis of EH, for example, hypomethylation of interleukin‐6 ( IL‐6 ), angiotensin II type 1 receptor ( AGTR1 ), angiotensin‐converting enzyme ( ACE ), Na+/K+/Cl− cotransporter protein 1 ( NKCC1 ), and α‐adducin ( ADD1 ), and the hypermethylation of 11β‐hydroxysteroid dehydrogenase type II ( 11β‐HSD‐2 ) …”

Section: Introductionmentioning

confidence: 99%

“…important contributor to the pathogenesis of EH, for example, hypomethylation of interleukin-6 (IL-6), 6 angiotensin II type 1 receptor (AGTR1), 7 angiotensin-converting enzyme (ACE), 8 Na+/K+/Cl− cotransporter protein 1 (NKCC1), 9 and α-adducin (ADD1), 10 and the hypermethylation of 11β-hydroxysteroid dehydrogenase type II (11β-HSD-2). 11 Serine hydroxymethyltransferase 1 (SHMT1), located on chromosome 17p11.2, is a key enzyme involved in folic acid metabolism.…”

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confidence: 99%

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Serine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension

Wang

Ying

et al. 2018

Clinical Laboratory Analysis

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Background Serine hydroxymethyltransferase 1 (SHMT1) is an enzyme involved in folic acid metabolism and is known to contribute to the development of hypertension. We evaluated the relationship between SHMT1 promoter methylation and essential hypertension (EH). Methods Quantitative methylation‐specific polymerase chain reaction was used to measure the SHMT1 promoter methylation level in 241 EH patients and 288 age‐ and gender‐matched healthy individuals. The diagnostic value of SHMT1 promoter hypermethylation was analyzed using a receiver operating characteristic (ROC) curve. The Gene Expression Omnibus (GEO) database and dual‐luciferase reporter assay were used to validate our findings. Results Compared with the control group, significant differences in SHMT1 promoter methylation were found in both EH and hyperhomocysteinemia groups (P < 0.001 and P = 0.029, respectively). The area under the curve of the diagnosis of SHMT1 promoter hypermethylation for EH was 0.808, with a sensitivity and specificity of 73.9% and 77.8%, respectively. The risk of SHMT1 promoter hypermethylation was significantly higher in the >65‐year group than in the ≤65‐year group (odds ratio = 3.925; 95% confidence interval = 2.141‐7.196). In addition, GEO database analysis showed that 5‐aza‐deoxycytidine increased gene expression in several carotid endothelial cell lines. A dual‐luciferase reporter assay revealed that the target sequence in the SHMT1 promoter upregulated gene expression. Conclusion Our findings indicate that SHMT1 promoter hypermethylation increases the risk of EH and may be a promising biomarker for EH.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Serine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension

Wang

Ying

et al. 2018

Clinical Laboratory Analysis

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“…Accumulating evidence indicates that IFN-γ, the first cytokine identified in endothelial cells, induces the expression of major histocompatibility complex genes and enhances the antiviral activity of immune cells (Lubina-Dąbrowska et al 2017). Furthermore, some studies revealed that the methylation of proinflammatory-cytokine genes is associated with blood pressure, e.g., genes of C-reactive protein, IL-6, IL-1 beta (IL-1β), and tumor necrosis factor α (Sullivan et al 2007;Lópezjaramillo et al 2008;Bay-Richter et al 2012;Mao et al 2017b). However, the methylation status of IFNG among EH patients remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Hypomethylation of the Interferon <i>γ</i> Gene as a Potential Risk Factor for Essential Hypertension: A Case-Control Study

Bao

Mao²,

et al. 2018

Tohoku J. Exp. Med.

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Essential hypertension (EH) is a multifactorial disease. Interferon-γ (IFN-γ) plays an important role in the onset of EH through cytokine-mediated systemic inflammatory responses. We aimed to determine whether the methylation status of the IFN-γ gene (IFNG) promoter is involved in the pathogenesis of EH. Six copies of CpG dinucleotides are distributed between 3,203 bp and 3,121 bp upstream from the transcription initiation site of IFNG, termed CpG1 to CpG6 in the 5'-to-3' direction. We recruited 96 patients with EH and 96 sex- and age-matched healthy subjects as controls. Using bisulfate pyrosequencing datasets, we analyzed the methylation status of the six CpG sites and thus found that CpG5 was consistently methylated in all of the 96 EH patients and 96 control subjects. Among the remaining five CpG sites, there was no significant difference in the methylation levels of CpG4 and CpG6 between the two groups. By contrast, CpG1 (P = 0.003) and CpG3 (P = 5.87 × 10) were highly methylated among the EH subjects compared with the controls, whereas CpG2 (P = 1.24 × 10) was significantly less methylated in among EH subjects. The methylation levels of CpG2 were still lower after adjustment with logistic regression (adjusted P = 0.032). The CpG2 methylation level was an effective marker of EH (area under curve = 0.384; P = 1.40 × 10). The present study shows that hypomethylation of the IFNG promoter is significantly related to the risk of EH, providing new insights into the pathogenesis of EH.

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“…Studies show that hypomethylation mechanisms can lead to higher ACE, β‐adrenergic receptors and Na + channel expression in the hypertensive condition . In agreement with this, it was recently demonstrated that the hypo‐methylation process of the angiotensin II type I receptor (AGTR1) and interleukin‐6 gene in peripheral blood DNA, increase the risk of essential hypertension in human.…”

Section: Epigenetic Modifications: a Potential Pathway Linking Maternmentioning

confidence: 59%

Maternal protein malnutrition induced‐hypertension: New evidence about the autonomic and respiratory dysfunctions and epigenetic mechanisms

Alves

Costa‐Silva

2017

Clin Exp Pharma Physio

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SummaryMaternal protein malnutrition during the critical stages of development (pregnancy, lactation and first infancy) can lead to adult hypertension. Studies have shown that renal and cardiovascular dysfunctions can be associated to the development of hypertension in humans and rats exposed to maternal protein malnutrition. The etiology of hypertension, however, includes a complex network involved in central and peripheral blood pressure control. Recently, the hyperactivity of the sympathetic nervous system in protein-restricted rats has been reported. Studies have shown that protein malnutrition during pregnancy and/or lactation alters blood pressure control through mechanisms that include central sympathetic-respiratory dysfunctions and epigenetic modifications, which may contribute to adult hypertension. Thus, this review will discuss the historical context, new evidences of neurogenic disruption in respiratorysympathetic activities and possible epigenetic mechanisms involved in maternal protein malnutrition induced-hypertension. K E Y W O R D Shypertension, malnutrition, phenotypic plasticity, sympathetic activity, ventilation | INTRODUCTIONArterial hypertension (AH) affects more than 1 billion people around the world and is a major risk factor for cardiovascular dysfunction, recognized as the main cause of morbidity and mortality. Because of the interaction between the sympathetic and respiratory nervous systems, growing evidence supports the notion that an increase in sympathetic and respiratory activities plays an important role in the development of hypertension. [8][9][10] This observation has prompted the development of several studies evaluating sympathetic and respiratory activities and sensitivity of peripheral and central chemoreceptors in various hypertension models. For example, in chronic intermittent hypoxia 8,11 in spontaneously hypertensive rats (SHR) 4 and in renovascular hypertension, 12 augmented sympathetic-respiratory activities and higher peripheral chemosensitivity were seen to be associated to hypertension.

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Hypomethylation of interleukin-6 (IL-6) gene increases the risk of essential hypertension: a matched case–control study

Cited by 32 publications

References 39 publications

Serine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension

Serine hydroxymethyltransferase 1 promoter hypermethylation increases the risk of essential hypertension

Hypomethylation of the Interferon <i>γ</i> Gene as a Potential Risk Factor for Essential Hypertension: A Case-Control Study

Maternal protein malnutrition induced‐hypertension: New evidence about the autonomic and respiratory dysfunctions and epigenetic mechanisms

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