SCN5A gene and prolonged QT in sickle cell disease

SCN5A基因与镰状细胞病中QT间期延长

• 批准号: 9109064
• 负责人: JOSEPH F MAHER
• 金额: $ 35.73万
• 依托单位: UNIVERSITY OF MISSISSIPPI MED CTR
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-10 至 2020-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9109064
• 关键词: Address; Adult; African American; Cardiac; Cardiomyopathies; Child; Childhood; Clinic; Clinical; Communities; Creatinine; DNA; Data; Echocardiography; Electrocardiogram; Environmental Risk Factor; Ferritin; Future; Genes; Genetic; Genotype; Goals; Health; Hemolysis; Hereditary Disease; Hypokalemia; Individual; Iron Overload; Jackson Heart Study; Kidney Failure; Laboratories; Life Expectancy; Long QT Syndrome; Measures; Medical center; Methadone; Mississippi; National Heart, Lung, and Blood Institute; Other Genetics; Outcome; Oxycodone; Participant; Patients; Personal Satisfaction; Pharmaceutical Preparations; Predisposing Factor; Predisposition; Premature Mortality; Prevalence; Pulmonary Hypertension; Recruitment Activity; Reporting; Research; Risk; Risk Factors; Role; Sampling; Serum; Sickle Cell Anemia; Sodium Channel; Testing; Torsades de Pointes; Tricuspid Valve Insufficiency; Universities; Variant; Ventricular Tachycardia; base; genetic variant; health disparity; high risk; male; mortality; mortality disparity; population based; social; sudden cardiac death; therapy development

DESCRIPTION (provided by applicant): Sickle cell disease (SCD) is a common genetic disorder in African Americans, with a major impact on health and social well-being and a life expectancy of only 42 years. Individuals with SCD are known to be at increased risk of sudden cardiac death, the basis of which is not well understood. Investigating the genetic and environmental factors that contribute to sudden cardiac death in SCD should allow development of interventions aimed at reducing this health disparity in early mortality. We have recently reported a study showing that SCN5A-1103Y interacts with hypokalemia to promote LQT in a community-based population of African Americans, within the NHLBI Jackson Heart Study (JHS). However, whether SCN5A-1103Y or other genetic variants interact with the other QT-prolonging factors present in individuals with SCD, to contribute to LQT and the risk of sudden cardiac death, has not been studied before. At the University of Mississippi Medical Center, we have large pediatric and adult SCD clinics with over 1,200 patients, drawn from the same general community as participants in the JHS. We propose to study the interaction of SCN5A-1103Y and other genetic variants, with QT-prolonging factors present in SCD, on risk of LQT. This will provide a basis for future studies of the importance of the interaction of these genetic and secondary factors on clinical outcomes and management, with the long-term goal of decreasing the health disparity in mortality in individuals with SCD.

描述（由申请人提供）：镰状细胞病（SCD）是非裔美国人常见的遗传性疾病，对健康和社会福祉有重大影响，预期寿命仅为42岁。已知患有SCD的个体具有增加的心源性猝死风险，其基础尚不清楚。调查导致SCD患者心源性猝死的遗传和环境因素应有助于制定旨在减少早期死亡率中这种健康差异的干预措施。 我们最近在NHLBI杰克逊心脏研究（JHS）中报道了一项研究，该研究显示SCN 5A-1103 Y与低钾血症相互作用，促进非裔美国人社区人群的LQT。然而，SCN 5A-1103 Y或其他遗传变异是否与SCD患者中存在的其他QT延长因子相互作用，从而导致LQT和心源性猝死的风险，以前尚未研究过。 在密西西比大学医学中心，我们有大型的儿科和成人SCD诊所，有超过1,200名患者，来自与JHS参与者相同的普通社区。我们建议研究SCN 5A-1103 Y和其他遗传变异与SCD中存在的QT延长因子的相互作用对LQT风险的影响。这将为未来研究这些遗传和次要因素对临床结局和管理的相互作用的重要性提供基础，其长期目标是减少SCD患者死亡率的健康差异。