SCN5A gene and prolonged QT in sickle cell disease

描述(申请人提供)：镰状细胞病(SCD)是一种在非裔美国人中常见的遗传疾病，对健康和社会福祉有重大影响，预期寿命只有42岁。众所周知，SCD患者心源性猝死的风险增加，其基础尚不清楚。对导致SCD心源性猝死的遗传和环境因素进行调查，应该可以开发出旨在减少早期死亡率的健康差距的干预措施。我们最近报道的一项研究表明，在NHLBI杰克逊心脏研究(JHS)中，SCN5A-1103Y与低钾血症相互作用，在以社区为基础的非裔美国人中促进LQT。然而，SCD个体中存在的SCN5A-1103Y或其他基因变异是否与其他QT延长因子相互作用，从而导致LQT和心源性猝死的风险，以前还没有研究过。在密西西比大学医学中心，我们有大型的儿童和成人SCD诊所，有1200多名患者，他们来自与JHS参与者相同的普通社区。我们建议研究SCN5A-1103Y和其他遗传变异与SCD中存在的QT延长因子对LQT风险的交互作用。这将为未来研究这些遗传因素和次要因素对临床结果和管理的相互作用的重要性提供基础，长期目标是减少SCD患者死亡率的健康差异。

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.