Advertisement

Topics

Genetic Determinants of Sudden Cardiac Death

2014-07-23 21:52:20 | BioPortfolio

Summary

To evaluate whether sequence variants and selected cardiac ion channel genes are associated with risk of sudden cardiac death in the general population.

Description

BACKGROUND:

Sudden cardiac death (SCD) affects 400,000 individuals each year in the U.S. alone. Over half have no evidence of heart disease prior to death, and the ability to identify those at risk and therefore prevent SCD is poor. Mutations in cardiac ion channel genes including SCN5A, KVLQT1, HERG, KCNE1, KCNE2, and RyR2 have been implicated in monogenic traits with a high risk of SCD, such as the long-QT, Brugada, sudden infant death syndrome, and catecholaminergic polymorphic ventricular tachycardia. Alterations in ion channel function can result in life-threatening ventricular arrhythmias in diverse disease states. Therefore, sequence variants in these genes that alter function or transcription of these ion channels may confer a predisposition to ventricular arrhythmia and SCD in broader populations.

DESIGN NARRATIVE:

This study will determine if sequence variants in the cardiac ion channel genes are associated with an increased risk of sudden cardiac death in apparently healthy populations. Cases of sudden cardiac death will be assembled from five NIH-funded prospective cohorts with a total of 106,314 individuals with existent blood samples. All cohorts are exceptionally well characterized with respect to environmental exposures and have collected medical records on cardiovascular endpoints. The investigators will characterize all coding sequence variation and selected non-coding sequence variation among 100 cases and controls from these cohorts. Using these novel markers, they will define the haplotype block structure (SNPs in linkage disequilibrium) for the six cardiac ion channel genes, including SCN5A, KVLQT1, HERG, KCNE1, KCNE2, and RyR2. They will then employ a nested case-control design and conditional logistic regression to test for associations between haplotypes (haplotype tag SNPs) in both coding and non-coding regions and sudden cardiac death risk. They will also test directly for associations between single loci that may have functional significance and sudden cardiac death risk. An estimated 600 cases of well-documented sudden cardiac death will be confirmed over the first three years of the grant period, and these cases will be matched on age, sex, ethnicity, and geographic location to two control subjects from the same cohort. In addition, based upon known sex-differences in the phenotypic expression of the candidate genes in the primary arrhythmic disorders, the investigators will specifically examine sex-differences in the risk of sudden cardiac death associated with sequence variation in these genes. The findings generated will have substantial implications for our understanding of the sudden cardiac death syndrome and risk stratification in the general population.

Study Design

N/A

Conditions

Cardiovascular Diseases

Status

Completed

Source

National Heart, Lung, and Blood Institute (NHLBI)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-07-23T21:52:20-0400

Clinical Trials [1214 Associated Clinical Trials listed on BioPortfolio]

Cardiovascular Diseases in HIV-infected Subjects (HIV-HEART Study)

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...

The Effects of Aerobic Exercise in Microvascular Endothelium Function in Patients With Cardiovascular Diseases

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...

ARROW:identificAtion of postpRandial biomaRkers tOWards Cardiovascular Prevention

The purpose of this study is to better understand the association between the postprandial biomarker responses after a food challenge with the development of cardiovascular diseases in hea...

Development, Testing, and Validation of A Protocol To Assess Cardiovascular Reactivity in Human Populations

To develop a comprehensive protocol for assessing cardiovascular reactivity to stressors, for use in epidemiological and clinical investigations of cardiovascular diseases in healthy popul...

Cardiovascular Diseases in the Silesian Region in Poland.

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...

PubMed Articles [11671 Associated PubMed Articles listed on BioPortfolio]

Association between alexithymia and risk of incident cardiovascular diseases in the SUpplémentation en Vitamines et Minéraux AntioXydants (SU.VI.MAX) Cohort.

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...

12-year trends in cardiovascular risk factors (2002-2005 through 2011-2014) in patients with cardiovascular diseases: Tehran lipid and glucose study.

To examine the trend of cardiovascular diseases (CVD) risk factors among a Middle Eastern population with prevalent CVD during a median follow up of 12 years.

Lipidomic insight into cardiovascular diseases.

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...

Introduction and Update on Obesity and Cardiovascular Diseases 2018.

Human Emotions on the Onset of Cardiovascular and Small Vessel Related Diseases.

The aim of the present study was to examine the relation between understanding of emotions and cardiovascular related diseases, namely coronary heart disease, diabetes mellitus and obesity. The unique...

Medical and Biotech [MESH] Definitions

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.

More From BioPortfolio on "Genetic Determinants of Sudden Cardiac Death"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topic

Cardiology
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...


Searches Linking to this Trial