Hypomethylation of the Angiotensin II Type I Receptor (AGTR1) Gene Along with Environmental Factors Increases the Risk for Essential Hypertension

Objectives: The present study aimed to evaluate the hypertension status of community residents, analyze environmental and epigenetic factors, and propose prevention measures for hypertension. Methods: In our study, different methylation levels were distinguished utilizing melting temperature (Tm) values in both the case and the control group. Multiple logistic regression analysis was used to estimate the risk of having essential hypertension (EH) between hypertensive and nonhypertensive participants. A receiver-operating characteristic curve was used to analyze Tm cutoff levels of methylation. Results: The average DNA Tm was 71.784 with a standard deviation of 0.210. The Tm value of community residents (Fujian, China) was inversely correlated with systolic and diastolic blood pressure. Student t test analysis showed a clear separation in Tm expression levels between the hypertensive and the control group (p < 0.05). The Tm value was lower in the hypertension group than in the normotensive group. Multivariate regression analysis showed that high levels of DNA methylation were a protective factor in hypertension with adjustment of demographic and environmental factors, whereas when the Tm value increased by 0.1 units, the risk of hypertension was reduced by 0.652 times. Patients that smoked and consumed an irregular diet demonstrated a lower degree of methylation in the presence of hypertension. Conclusions: DNA methylation affects the risk for the development of hypertension; therefore, epigenetic markers could be used to measure hypertension levels to help elucidate the pathogenesis of EH.

[1]  I. Hajjar,et al.  Hypertension: trends in prevalence, incidence, and control. , 2006, Annual review of public health.

[2]  K. Nakai,et al.  Genome-Wide Analysis of DNA Methylation and Expression of MicroRNAs in Breast Cancer Cells , 2012, International journal of molecular sciences.

[3]  I. Bogdarina,et al.  Epigenetic Modification of the Renin-Angiotensin System in the Fetal Programming of Hypertension , 2007, Circulation research.

[4]  H. Möller,et al.  DNA Methylation Analysis of the Angiotensin Converting Enzyme (ACE) Gene in Major Depression , 2012, PloS one.

[5]  Jiang He,et al.  Primary prevention of hypertension: clinical and public health advisory from The National High Blood Pressure Education Program. , 2002, JAMA.

[6]  D. Cusi,et al.  Two point mutations within the adducin genes are involved in blood pressure variation. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[7]  A. Kondacs,et al.  The combination of homozygous MTHFR 677T and angiotensin II type-1 receptor 1166C variants confers the risk of small-vessel-associated ischemic stroke , 2007, Journal of Molecular Neuroscience.

[8]  M. Yang,et al.  The Effects of Calcium Channel Blockers in the Prevention of Stroke in Adults with Hypertension: A Meta-Analysis of Data from 273,543 Participants in 31 Randomized Controlled Trials , 2013, PloS one.

[9]  Lisa V. Smith,et al.  Utility of Anthropometric Measures in a Multiethnic Population: Their Association with Prevalent Diabetes, Hypertension and Other Chronic Disease Comorbidities , 2014, Journal of Community Health.

[10]  E. Ingelsson,et al.  Impact of Body Mass Index and the Metabolic Syndrome on the Risk of Cardiovascular Disease and Death in Middle-Aged Men , 2010, Circulation.

[11]  M. Mason,et al.  Receiver-operating characteristics of adiposity for metabolic syndrome: the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study , 2010, Public Health Nutrition.

[12]  N. Al-Baghli,et al.  Performance of body mass index in predicting diabetes and hypertension in the Eastern Province of Saudi Arabia , 2009, Annals of Saudi medicine.

[13]  G. Calin,et al.  miRNAs and long noncoding RNAs as biomarkers in human diseases , 2013, Expert review of molecular diagnostics.

[14]  A. Saremi,et al.  Alcohol consumption predicts hypertension but not diabetes. , 2004, Journal of studies on alcohol.

[15]  O. Olivieri,et al.  Epigenetic control of 11 beta-hydroxysteroid dehydrogenase 2 gene promoter is related to human hypertension. , 2008, Atherosclerosis.

[16]  R. Nyamdorj BMI Compared With Central Obesity Indicators in Relation to Diabetes and Hypertension in Asians , 2008, Obesity.

[17]  D. Gaudet,et al.  ABCA1 gene promoter DNA methylation is associated with HDL particle profile and coronary artery disease in familial hypercholesterolemia , 2012, Epigenetics.

[18]  J. Pogue,et al.  Waist circumference and waist-to-hip ratio as predictors of cardiovascular events: meta-regression analysis of prospective studies. , 2007, European heart journal.

[19]  M. Szyf,et al.  Developmental programming through epigenetic changes. , 2007, Circulation research.

[20]  A. Rosenthal,et al.  Variations in DNA methylation during mouse cell differentiation in vivo and in vitro. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[21]  S. Duan,et al.  Lower ADD1 Gene Promoter DNA Methylation Increases the Risk of Essential Hypertension , 2013, PloS one.

[22]  G. Bianchi,et al.  Renal Na,K-ATPase in genetic hypertension. , 1996, Hypertension.

[23]  R. Hui,et al.  Hypertensive epigenetics: from DNA methylation to microRNAs , 2015, Journal of Human Hypertension.

[24]  G. Bianchi,et al.  PST 2238 a new antihypertensive compound that modulates renal Na-KATPase in genetic hypertension. , 1999 .

[25]  F. Frey,et al.  Epigenetic regulation of 11β-hydroxysteroid dehydrogenase type 2 expression , 2004 .

[26]  M. Winniford,et al.  Cigarette smoking increases sympathetic outflow in humans. , 1998, Circulation.

[27]  I. Bogdarina,et al.  Investigation of the role of epigenetic modification of the rat glucokinase gene in fetal programming. , 2004, Life sciences.

[28]  P. Manunta,et al.  Evidence for an interaction between adducin and Na+-K+-ATPase: relation to genetic hypertension. , 1999, American journal of physiology. Heart and circulatory physiology.

[29]  Mika Kivimäki,et al.  Risk Models to Predict Hypertension: A Systematic Review , 2013, PloS one.

[30]  T. Thum,et al.  Epigenetic modifications in cardiovascular disease , 2012, Basic Research in Cardiology.

[31]  M. Aries,et al.  Interarm blood pressure difference and vascular disease , 2012, The Lancet.

[32]  H. Sesso,et al.  Body Mass Index and Vigorous Physical Activity and the Risk of Heart Failure Among Men , 2009, Circulation.

[33]  C. N. Hales,et al.  Gluconeogenesis, glucose handling, and structural changes in livers of the adult offspring of rats partially deprived of protein during pregnancy and lactation. , 1997, The Journal of clinical investigation.

[34]  A. Binder A review of the genetics of essential hypertension , 2007, Current opinion in cardiology.

[35]  Su-Hyung Hong,et al.  Promoter hypomethylation upregulates Na+-K+-2Cl- cotransporter 1 in spontaneously hypertensive rats. , 2010, Biochemical and biophysical research communications.

[36]  G. Mancia,et al.  Sympathetic activation in obese normotensive subjects. , 1995, Hypertension.

[37]  I. Bogdarina,et al.  Characterization of the angiotensin (AT1b) receptor promoter and its regulation by glucocorticoids , 2009, Journal of molecular endocrinology.

[38]  M. Franco,et al.  Modification of Epigenetic Patterns in Low Birth Weight Children: Importance of Hypomethylation of the ACE Gene Promoter , 2014, PloS one.

[39]  M. Barciszewska,et al.  Global DNA methylation changes in blood of patients with essential hypertension. , 2010, Medical science monitor : international medical journal of experimental and clinical research.

[40]  S. Kjeldsen,et al.  Polymorphisms in Candidate Genes for Blood Pressure Regulation in Young Men with Normal or Elevated Screening Blood Pressure , 2001, Blood pressure.

[41]  D. Vieau,et al.  Epigenetic regulation of somatic angiotensin-converting enzyme by DNA methylation and histone acetylation , 2011, Epigenetics.