Design of a Controlled Trial of Cascade Screening for Hypercholesterolemia: The (CASH) Study
Design of a Controlled Trial of Cascade Screening for Hypercholesterolemia: The (CASH) Study
复制标题
DOI：
10.3390/jpm8030027
复制
发表时间：
2018-09-01
影响因子：
--
通讯作者：
Bailey, Kent R.
中科院分区：
文献类型：
--
作者：
Kullo, Iftikhar J.;Bailey, Kent R.
为了为家族性高胆固醇血症 (FH) 患者家庭成员的筛查提供指导，我们设计了一项临床试验来比较具有和不具有可识别致病性变异的 FH 患者的级联筛查效果。患有高胆固醇血症（低密度脂蛋白胆固醇 (LDL-C) > 155 mg/dL）的参与者接受了 LDLR、APOB 和 PCSK9 测序以及与 LDL-C 相关的 6 个单核苷酸多态性的基因分型，然后计算 LDL-C 的多基因评分。我们鉴定了 24 名确诊 FH 患者（三个 FH 基因之一存在致病变异）、76 名可能 FH 患者（荷兰血脂临床网络 (DLCN) 评分 > 6，无致病变异）和 262 名可能 FH 患者（DLCN 评分 3-5，无致病变异）。我们将招募 50 名确诊 FH 患者，从 Mayo 的 FH 诊所另外招募 26 名患者，以及各 50 名疑似和可能 FH 患者，年龄和性别相匹配。确诊 FH 患者的家庭成员将使用唾液试剂盒接受相关致病变异检测，疑似 FH 患者的家庭成员将接受血脂分析。我们将评估可能/可能的 FH 患者的家庭成员中检测到的新病例数（定义为明确 FH 患者的家庭成员中存在致病性变异或 LDL-C > 155 mg/dL（儿童中 > 130 mg/dL），以及检测新病例的成本。拟议的临床试验将比较对有/无可识别致病性变异的 FH 患者进行级联筛查的产量和成本，从而为 FH 级联筛查提供指导。
To inform guidelines for screening family members of patients with familial hypercholesterolemia (FH), we designed a clinical trial to compare the yield of cascade screening in FH patients with and without an identifiable pathogenic variant. Participants with hypercholesterolemia (Low-density lipoprotein cholesterol (LDL-C) > 155 mg/dL) underwent sequencing of LDLR, APOB, and PCSK9 and genotyping of six single nucleotide polymorphisms associated with LDL-C followed by calculation of a polygenic score for LDL-C. We identified 24 patients with definite FH (pathogenic variant in one of the three FH genes), 76 patients with probable FH (Dutch lipid clinic network (DLCN) score > 6, no pathogenic variant), and 262 patients with possible FH (DLCN score 3-5, no pathogenic variant). We will enroll 50 patients with definite FH by recruiting an additional 26 from the FH Clinic at Mayo and 50 patients each with probable and possible FH, matching on age and sex. Family members of patients with definite FH will undergo testing for the relevant pathogenic variant using saliva kits and family members of those with probable/possible FH will have a lipid profile checked. We will assess the number of new cases detected (defined as presence of a pathogenic variant in the family member of definite FH patient or LDL-C > 155 mg/dL (>130 mg/dL in children) in family members of probable/possible FH patients, and the cost of detecting a new case. The proposed clinical trial will compare the yield and cost of cascade screening for FH patients with/without an identifiable pathogenic variant, and thereby inform guidelines for cascade screening for FH.