DNA methylation and hypertension: emerging evidence and challenges

Han, Liyuan; Liu, Yanfen; Duan, Shiwei; Perry, Benjamin J.; Wen, Li; He, Yonghan

doi:10.1093/bfgp/elw014

Cited by 28 publications

(30 citation statements)

References 97 publications

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“…Lower levels of DNA methylation has been implicated in the development of atherosclerosis and hypertension . The association of lower diastolic blood pressure with LINE‐1 methylation found here and by Han et al is in keeping with our study. Pearce et al observed an association between LINE‐1 DNA methylation and fasting concentrations of glucose, triglycerides and total cholesterol, LDL and HDL cholesterol and also HDL:LDL ratio considered to be an increased risk biomarkers for cardiovascular diseases and Type 2 diabetes .…”

Section: So What Does It Mean?supporting

confidence: 93%

“…Pearce et al observed an association between LINE‐1 DNA methylation and fasting concentrations of glucose, triglycerides and total cholesterol, LDL and HDL cholesterol and also HDL:LDL ratio considered to be an increased risk biomarkers for cardiovascular diseases and Type 2 diabetes . Nevertheless, some other authors propose the role of epigenetics modification as a biomarker of CVD, independently of established risk factors . The association between the degree of LINE‐1 methylation status and decrease in cholesterol/HDL cholesterol ratio over time suggests a complex interaction between DNA methylation and the other factors, principally statin prescription.…”

Section: So What Does It Mean?mentioning

confidence: 99%

“…11 Nevertheless, some other authors propose the role of epigenetics modification as a biomarker of CVD, independently of established risk factors. 9 The association between the degree of LINE-1 methylation status and decrease in cholesterol/HDL cholesterol ratio over time suggests a complex interaction between DNA methylation and the other factors, principally statin prescription. Importantly by the end of the follow-up period, 91.6% of patients were being prescribed one or the other lipid lowering therapies.…”

Section: So What Doe S It Me An?mentioning

confidence: 99%

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Assessment of global long interspersed nucleotide element‐1 ( LINE ‐1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2 DM ) individuals

Malipatil

Narayanan²,

Siddals

et al. 2018

Int J Clin Pract

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Introduction Recent studies have indicated that methylation of the LINE‐1 elements is associated with an increased risk of worsening carbohydrate metabolism. It has been shown that overall DNA methylation of LINE‐1 elements could be considered as a risk factor for T2DM and its complications, independent of other established risk factors. Methods A total of 794 T2DM individuals from Salford, UK were included in this study (60% men n = 470). All patients had clinical and metabolic variables measured in 2002 (baseline outcomes) and annually through to 2016. Global LINE‐1 DNA methylation was measured at four CpG sites. The QIAGEN PyroMark Q96 MD pyrosequencer was used to quantify methylation. Results The overall mean ± SD global LINE‐1 methylation was 75.81 ± 3.25%. Cross‐sectional linear regression analysis at baseline year 2002 showed that LINE‐1 methylation was a significant predictor of diastolic BP (adjusted beta coefficient β = −0.25), estimated glomerular filtration rate (eGFR) (β = −0.48) and cholesterol HDL ratio (β = −0.04). A 10% increase in LINE‐1 methylation was associated with a lower diastolic BP by 2.5 mm Hg, a lower eGFR by 4.8 ml/min/1.73 m2 and decreased cholesterol/HDL ratio by 0.4 mmol/L. Longitudinal analysis over the 14‐year‐follow‐up periods showed that global LINE‐1 methylation at baseline was associated with lower BMI in women [β = −0.25] and lower cholesterol: HDL ratio [β = −0.07]. A 10% increase in LINE‐1 methylation was associated with reduction in BMI by 2.5 kg/m2 in women and reduction in cholesterol:HDL ratio by 0.7 mmol/L. Conclusion In a 14‐year longitudinal cohort of T2DM individuals, relations between global LINE‐1 DNA methylation status and specific metabolic markers were seen. Also, a higher degree of DNA methylation was predictive of less weight gain over time in women.

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Section: So What Does It Mean?supporting

confidence: 93%

Section: So What Does It Mean?mentioning

confidence: 99%

Section: So What Doe S It Me An?mentioning

confidence: 99%

See 1 more Smart Citation

Assessment of global long interspersed nucleotide element‐1 ( LINE ‐1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2 DM ) individuals

Malipatil

Narayanan²,

Siddals

et al. 2018

Int J Clin Pract

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“…It is possible therefore that intrinsic differences in the relative activity of 11‐βHSD2, 11‐βHSD1, and the cortisol reductases contribute to the variation in metabolism seen in these patients. Such differences may be caused by genetic differences affecting expression or activity, such as the polymorphisms in 11‐βHSD2 that associate with hypertension, 34 or epigenetic variation, as studies in rats and in humans have shown differential methylation of the 11‐βHSD2 locus is associated with hypertension 35–37 . Whilst the examples given affect 11‐βHSD2 activity, genetic and epigenetic variation at other loci may also contribute to differences in cortisol metabolism.…”

Section: Discussionmentioning

confidence: 99%

Metabolic profiling shows pre‐existing mitochondrial dysfunction contributes to muscle loss in a model of ICU‐acquired weakness

Kemp

Paúl

Hinken

et al. 2020

J cachexia sarcopenia muscle

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Background Surgery can lead to significant muscle loss, which increases recovery time and associates with increased mortality. Muscle loss is not uniform, with some patients losing significant muscle mass and others losing relatively little, and is likely to be accompanied by marked changes in circulating metabolites and proteins. Determining these changes may help understand the variability and identify novel therapeutic approaches or markers of muscle wasting. Methods To determine the association between muscle loss and circulating metabolites, we studied 20 male patients (median age, 70.5, interquartile range, 62.5-75) undergoing aortic surgery. Muscle mass was determined before and 7 days after surgery and blood samples were taken before surgery, and 1, 3, and 7 days after surgery. The circulating metabolome and proteome were determined using commercial services (Metabolon and SomaLogic). Results Ten patients lost more than 10% of the cross-sectional area of the rectus femoris (RF CSA) and were defined as wasting. Metabolomic analysis showed that 557 circulating metabolites were altered following surgery (q < 0.05) in the whole cohort and 104 differed between wasting and non-wasting patients (q < 0.05). Weighted genome co-expression network analysis, identified clusters of metabolites, both before and after surgery, that associated with muscle mass and function (r = À0.72, p = 6 × 10 À4 with RF CSA on Day 0, P = 3 × 10 À4 with RF CSA on Day 7 and r = À0.73, P = 5 × 10 À4 with hand-grip strength on Day 7). These clusters were mainly composed of acyl carnitines and dicarboxylates indicating that pre-existing mitochondrial dysfunction contributes to muscle loss following surgery. Surgery elevated cortisol to the same extent in wasting and non-wasting patients, but the cortisol:cortisone ratio was higher in the wasting patients (Day 3 P = 0.043 and Day 7 P = 0.016). Wasting patients also showed a greater increase in circulating nucleotides 3 days after surgery. Comparison of the metabolome with inflammatory markers identified by SOMAscan® showed that pre-surgical mitochondrial dysfunction was associated with growth differentiation factor 15 (GDF-15) (r = 0.79, P = 2 × 10 À4) and that GDF-15, interleukin (IL)-8), CC motif chemokine 23 (CCL-23), and IL-15 receptor subunit alpha (IL-15RA) contributed to metabolic changes in response to surgery. Conclusions We show that pre-existing mitochondrial dysfunction and reduced cortisol inactivation contribute to muscle loss following surgery. The data also implicate GDF-15 and IL-15RA in mitochondrial dysfunction.

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“…Notably, 5-methylcytosine (5mC) DNA methylation is a stable and inheritable epigenetic modification. Aberrant 5mC DNA methylation is the most well-defined epigenetic modification that regulates gene transcription affecting the pathogenesis, duration, and severity of essential hypertension [10,11]. For example, decreased global 5mC level in peripheral blood is correlated with increased essential hypertension severity [11,12].…”

Section: Introductionmentioning

confidence: 99%

DNA N6-methyladenine modification in hypertension

Guo

Pei

et al. 2020

Aging

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DNA methylation has a role in the pathogenesis of essential hypertension. DNA N6-methyladenine (6mA) modification as a novel adenine methylation exists in human tissues, but whether it plays a role in hypertension development remains unclear. Here, we reported that the global 6mA DNA level in leukocytes was significantly reduced in patients with hypertension and was reversed with successful treatment. Age, systolic blood pressure, and serum total cholesterol and high-density lipoprotein levels were associated with decreased leukocyte 6mA DNA level. Elevated ALKBH1 (AlkB homolog 1), a demethylase of 6mA, level mediated this dynamic change in 6mA level in leukocytes and vascular smooth muscle cells in hypertension mouse and rat models. Knockdown of ALKBH1 suppressed angiotensin II-induced vascular smooth muscle phenotype transformation, proliferation and migration. ALKBH1-6mA directly and negatively regulated hypoxia inducible factor 1 α (HIF1α), which responded to angiotensin II-induced vascular remodeling. Collectively, our results demonstrate a potential epigenetic role for ALKBH1-6mA regulation in hypertension development, diagnosis and treatment.

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DNA methylation and hypertension: emerging evidence and challenges

Cited by 28 publications

References 97 publications

Assessment of global long interspersed nucleotide element‐1 ( LINE ‐1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2 DM ) individuals

Assessment of global long interspersed nucleotide element‐1 ( LINE ‐1) DNA methylation in a longitudinal cohort of type 2 diabetes mellitus (T2 DM ) individuals

Metabolic profiling shows pre‐existing mitochondrial dysfunction contributes to muscle loss in a model of ICU‐acquired weakness

DNA N6-methyladenine modification in hypertension

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