Track topics on Twitter Track topics that are important to you
To localize, identify, and evaluate common polymorphic variation in genes involved in determining interindividual differences in blood pressure (BP) levels and essential hypertension status in three racial groups: African-Americans, Mexican-Americans, and Non-Hispanic Whites. The study consists of a six grant network, which in turn is part of an NHLBI initiative, the Family Blood Pressure Program (FBPP) consisting of four networks.
Hypertension, a complex disease involving the interplay of genetic and environmental factors, affects an estimated 50 million Americans and is a major predisposing factor for myocardial infarction, vascular disease, stroke, and renal failure. It has been estimated from segregation analysis and twin studies that approximately 45 percent of the interindividual differences in blood pressure are accounted for by genetic differences. The identification of the genes whose variants contribute to high blood pressure will have far-reaching effects on our understanding of the pathophysiology of the circulation and may suggest new preventive measures and rational therapeutic approaches.
One of the principal advantages of the genetic approach is that it identifies primary molecular defects. As a result, it will be possible to stratify the general hypertensive population into subgroups based on genotype and intermediate phenotype and thereby evaluate preventive strategies and therapeutic approaches in more homogeneous groups. In addition, the identification of hypertensive genes also provides the basis for an understanding of the interactions between genes and environmental factors. It is very likely that particular environmental variables exert their effects only in the presence of certain genotypes.
Until recently, the techniques for dissecting the genetic determinants of high blood pressure were not available or were not developed to an extent that would make the Family Blood Pressure Program initiative feasible. However, several recent advances in technology and analytical methods, together with the rapid construction of genetic maps, have substantially improved the chances of detecting these genetic factors.
The concept for the Family Blood Pressure Program was conceived in the Report of the Expert Panel on Genetic Strategies for Heart, Lung, and Blood Diseases. The initiative was approved by the Arteriosclerosis, Hypertension, and Lipid Metabolism Advisory Committee (AHLMAC) in March, 1993. The genetic-epidemiological aspects were approved by the Clinical Applications and Prevention Advisory Committee (CAPAC) in February, 1993. The Request for Applications was released in March, 1994. Awards were made in September, 1995.
GENOA, the Genetic Epidemiology Network of Arteriopathy, consists of a network of three field centers and biochemical and genetic core labs to study the common polymorphic genetic variations to determine individual differences in blood pressure and essential hypertension in 1,500 sibling pairs in three racial groups. Linkage analyses are performed using an extensive array of candidate genes and anonymous markers throughout the genome.
Each collaborating investigator is responsible for an essential element of the network: Eric Boerwinkle for genotyping and linkage analyses, Robert Ferrell for genotyping, Craig Hanis for recruiting Mexican-Americans, Richard Hutchinson for recruiting African-Americans, Sharon Kardia for cladistic and prediction analyses and data management, and Stephen Turner for recruiting Non-Hispanic whites and measuring physiologic variables. Between 1995 and 2000, the network carried out five specific aims to localize and characterize the genetic determinants of high blood pressure. Aim 1 used robust sibling pair linkage methods in 500 hypertensive sibling pairs in each racial group (a total of 1,500 sibling pairs) to localize genes influencing interindividual differences in the occurrence of essential hypertension. Aims 2 and 3 took advantage of previously collected blood pressure and intermediate predictor trait data from 1,488 normotensive sibling pairs from the Rochester Family Heart Study to localize genes contributing to essential hypertension. The linkage analyses (Aims 1-3) used both an extensive array of candidate genes and a large number of anonymous markers throughout the genome. Aim 4 used multiple diallelic sequence polymorphisms and cladistic analyses within a linked gene to identify haplotypes for further DNA sequencing in order to identify candidate functional DNA sequence variation contributing to interindividual differences in BP levels and essential hypertension status. Aim 5 evaluated the ability of candidate functional DNA sequence variation to predict essential hypertension status in the three racial groups.
The study was renewed in September 2000 to pursue two lines of investigation. The first was to identify and characterize genes contributing to atherosclerotic coronary heart disease using electron beam computed tomography (EBCT) to quantify coronary artery calcification as a measure of preclinical disease. Robust sibling-pair linkage methods were used to determine whether any of the more than 375 highly polymorphic tandem repeat marker loci spanning the genome were linked to genes influencing EBCT measures of coronary artery calcification in at least 500 GENOA sibships from Rochester, Minnesota. Association analysis was used to determine whether biallelic markers of DNA sequence variation in candidate genes identified by GENOA or others to influence blood pressure level or diagnostic category also influence EBCT measures of coronary artery calcification in at least 500 GENOA participants from Rochester, Minnesota. The second line of investigation extended analytical methods (linkage disequilibrium regression and combinatorial partitioning) to more finely localize positional candidate genes and loci, and to identifying gene-gene and gene-environment interaction effects influencing the measured Family Blood Pressure Program and GENOA phenotypes.
In the next phase of the FBPP extending the study through FY 2008, a major emphasis is placed on making the Program a shared resource for hypertension researchers in the United States and throughout the world. In Aim 1, the intestigators will build, maintain and update a publicly available knowledge-base to facilitate research by non-FBPP investigators on the genetics of hypertension, its risk factors and its complications. In Aim 2, they will use state-of-the-art genetic linkage analysis methods to identify additional linkage regions using subgroups of pedigrees and physiologically relevant combinations of phenotypes that will aid in localizing hypertension genes. In Aim 3, they will use a combination of bioinformatics, a dense array of SNPs, and state-of-the-art data analysis to follow-up regions of interest and identify the underlying hypertension genes. The regions to be followed-up include those identified during the current phase of the FBPP and Aim 2 of this renewal phase. In Aim 4, they will evaluate the hypertension genes identified in Aim 3 for their association with multiple measures reflecting the cardiovascular and renal complications of hypertension, including left ventricular mass and microalbuminuria. It is the long-term goal of the FBPP to have the hypertension genetics community develop a comprehensive picture of the genetic architecture of human hypertension, including its risk factors, complications, and response to treatment.
National Heart, Lung, and Blood Institute (NHLBI)
Published on BioPortfolio: 2014-08-27T03:57:57-0400
Human immunodeficiency virus (HIV) infection has been associated with a variety of cardiovascular diseases. Even most industrialised countries exhibit a growing and aging population of HIV...
This study evaluates the effects of different volumes of aerobic exercise training in cardiovascular parameters of patients with cardiovascular diseases enrolled in a cardiac rehabilitatio...
To develop a comprehensive protocol for assessing cardiovascular reactivity to stressors, for use in epidemiological and clinical investigations of cardiovascular diseases in healthy popul...
The Silesian Cardiovascular Database is an observational study of all patients hospitalized due to cardiovascular diseases. The date include information on the clinical characteristics, tr...
The incidence of cardiovascular diseases is still high and further efforts should be done in primary prevention. The main objective is to quantify the burden of subclinical atherosclerosis...
Cardiovascular diseases possess a major cause for fatality and disability the world over. Since last several decades, the rates of cardiovascular diseases-related deaths have decreased in a number of ...
Although alexithymia has been suggested to be associated with cardiovascular diseases, studies are scarce and a causal relationship is questionable. This study explored the prospective association bet...
Cardiovascular disease is a primary cause of mortality worldwide. Therefore, it is of major interest to identify sensitive molecular markers that predict cardiovascular events and point to therapeutic...
Evaluation of the effectiveness of risk management in persons with high cardiovascular risk is an important element in reducing the death rate of the population from cardiovascular diseases (CVD).
The fact that microRNAs play an important role in the development and pathogenesis of cardiovascular disease is beyond doubt. This article provides a brief overview of recent data that relate to micro...
Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.
Methods and procedures for the diagnosis of diseases or dysfunction of the cardiovascular system or its organs or demonstration of their physiological processes.
Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)
Dental care for patients with chronic diseases. These diseases include chronic cardiovascular, endocrinologic, hematologic, immunologic, neoplastic, and renal diseases. The concept does not include dental care for the mentally or physically disabled which is DENTAL CARE FOR DISABLED.
Blood pressure levels that are between normotension and hypertension. Individuals with prehypertension are at a higher risk for developing cardiovascular diseases. Generally, prehypertension is defined as SYSTOLIC PRESSURE of 131-139 mm Hg and/or DIASTOLIC PRESSURE of 81-89 when the optimal is 120/80 mm Hg. For diabetics and other metabolism diseases the prehypertension is around 110-129/70-79 mm Hg.
Cardiology is a specialty of internal medicine. Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...
Pulmonary arterial hypertension (PAH) is a chronic, life-threatening disorder characterized by abnormally high blood pressure in the arteries between the heart and lungs of affected individuals. Symptoms can range from mild breathles...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...