The genetic basis of essential hypertension.
ABSTRACT During the last few years the studies on the genetic basis of essential hypertension (EH) have been numerous, allowing however only a partial understanding of the underlying molecular mechanisms. The most used techniques were the candidate gene approach, genome-wide scanning, the intermediate phenotype approach and comparative-genomics in animal models. The renin-angiotensin-aldosterone system may play a prominent role in the genesis of hypertension, and polymorphisms of the genes coding for angiotensinogen, angiotensin-converting enzyme, angiotensin II type 1 and 2 receptors, and aldosterone synthase have been widely studied. Other mechanisms may involve the KLK 1 gene of tissue kallikrein, gene variants of endothelial nitric oxide synthase and polymorphisms of the endothelin-1 gene. Finally, a number of studies have highlighted the potential contribution of polymorphisms of genes coding for inflammatory cytokines, adrenergic receptors and intracellular G proteins, which can activate Na+/K+ exchangers. Further important information might derive from proteomic analysis and the study of mitochondrial genome. Overall, results have often been discordant, sometimes suggesting a different expression of the same gene variants in different populations. EH is a highly polygenic condition, caused by the combination of small changes in the expression of many genes, in conjunction with a variable collection of environmental factors.
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ABSTRACT: The present study aimed to investigate the incidence and predictors of hypertension in an Iranian adult population. Isfahan Cohort Study was a longitudinal population-based study that was conducted on adults aged 35 years or older, living in urban and rural areas of three districts in central Iran. After 7 years of follow-up, 3283 participants were re-evaluated using a standard protocol similar to the baseline. At both measurements, participants underwent medical interview, physical examination, and fasting blood measurements. Participants (n = 833) with prevalent hypertension were excluded from the analysis, resulting in a sample size of 2450. The participants' age was 47.3 ± 9.4 years (mean ± SD) and 50.7% were men. During the follow-up period, 542 (22.1%) individuals developed hypertension, 49.6% of whom were aware of their disease, 42.4% were treated, but only 24.9% were controlled. Incidence rates have shown no sex-specific difference across age and blood pressure (BP) categories. Multivariate-adjusted model controlled for all study covariates showed that age, male sex, general and central obesity, hypertriglyceridemia, impaired fasting glucose, diabetes mellitus, baseline BP at least 120/80 mmHg (nonoptimal BP), and parental history of hypertension independently contributed to the development of hypertension. Higher education level and more than 10% decrease in waist circumference over 7-year follow-up represented protective effects. In men, weight loss decreased and weight gain increased the risk of developing hypertension. Nonoptimal BP along with central obesity and hypertriglyceridemia together were responsible for 71% of the burden of hypertension. Our findings imply that there are other factors in addition to nonoptimal BP that deserve integrating into the risk assessment criteria for developing hypertension.Journal of Hypertension 09/2013; · 4.22 Impact Factor
Article: Epigenetics for Biomedical SciencesCornea 01/2009; 28. · 1.75 Impact Factor
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ABSTRACT: As a major cardiovascular risk factor for stroke, coronary artery disease, heart failure and end-stage renal disease, hypertension affects approximately one billion people and causes large economic burden worldwide. Cytochrome P450 3A5 (CYP3A5), belonging to the CYP3A subfamily, has been implicated in the regulation of blood pressure and may serve as a potential risk factor for the development of hypertension. Increased CYP3A5 activity could cause sodium and water retention by affecting the metabolism of cortisol in the kidneys. Furthermore, polymorphic CYP3A5 genotypes have been shown to cause differences in blood pressure response to antihypertensive drugs. Several studies have investigated the role of CYP3A5 in blood pressure response to amlodipine. However, recent data on the role of CYP3A5 in hypertension development and treatment are inconsistent. This review summarizes what is known regarding the relationship of CYP3A5 with hypertension, discusses the limitations in present studies, highlights the gaps and directs research to this field.Journal of Human Hypertension advance online publication, 18 July 2013; doi:10.1038/jhh.2013.67.Journal of human hypertension 07/2013; · 2.80 Impact Factor