A randomized controlled trial of genetic testing and cascade screening in familial hypercholesterolemia
A randomized controlled trial of genetic testing and cascade screening in familial hypercholesterolemia
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DOI：
10.1038/s41436-021-01192-z
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发表时间：
2021-05-26
影响因子：
8.8
通讯作者：
Rader, Daniel J.
中科院分区：
文献类型：
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作者：
Ajufo, Ezimamaka;DeGoma, Emil M.;Rader, Daniel J.
目的：对指数先证者进行以家族为基础的级联筛查被认为是识别未确诊的家族性高胆固醇血症（FH）个体的有效方法。先证者基因检测在FH级联筛查成功中的作用尚不清楚。方法我们将240例临床诊断为FH的患者随机分为FH基因检测组（n = 160）和常规治疗组（n = 80）。主要研究终点是在结果通知后一年内至少有一名亲属参加研究的先证者比例。结果先证者中位年龄59岁（47-67岁），女性占71%。只有28例（12%）先证者成功招募了亲属。虽然基因检测组与常规护理组（8.8%）相比，有亲属登记的先证者比例更高（13.1%），但这种差异并不显著（p = 0.40）。在亚组分析中，致病性变异组（22.7%）的亲属入组率高于无致病性变异组（9.5%）和常规治疗组（8.8%）（p = 0.04）。结论我们观察到，尽管对先证者反复推荐，但家庭参与级联筛查的比例很低。与常规护理相比，基因检测并没有改善家族参与FH级联筛查的情况。
Purpose Family-based cascade screening from index probands is considered an effective way of identifying undiagnosed individuals with familial hypercholesterolemia (FH). The role of genetic testing of the proband in the success of cascade screening for FH is unknown. Methods We randomized 240 individuals with a clinical diagnosis of FH to genetic testing for FH (n = 160) or usual care with lipid testing alone (n = 80). The primary study endpoint was the proportion of probands with at least one relative enrolled in the study within one year after the notification of results. Results Proband median age was 59 (47-67) and 71% were female. Only 28 (12%) probands succeeded in enrolling a relative. While the genetic testing group had a higher proportion of probands with relatives enrolled (13.1%) compared with the usual care group (8.8%), this difference was not significant (p = 0.40). In subgroup analyses, enrollment of a relative was higher in the pathogenic variant group (22.7%) compared to the no pathogenic variant (9.5%) and usual care groups (8.8%) (p = 0.04). Conclusion We observed a low rate of family participation in cascade screening despite repeated recommendations to probands. Compared to usual care, genetic testing did not improve family participation in cascade screening for FH.