Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world, multi-center, cohort study
Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world, multi-center, cohort study
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中国纯合子家族性高胆固醇血症：真实世界、多中心、队列研究的遗传和临床特征
DOI：
10.1016/j.jacl.2022.03.003
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发表时间：
2022-06-11
影响因子：
4.4
通讯作者：
Wang, Luya
中科院分区：
文献类型：
--
作者：
Jiang, Long;Stoekenbroek, Robert M.;Wang, Luya
背景资料：亚洲纯合子家族性高胆固醇血症（HoFH）患者的临床和基因型特征缺乏大规模数据。目的：确定中国大陆HoFH先证者的表型和遗传特征。方法：我们收集了2003年至2019年中国大陆10家临床医院疑似HoFH患者的数据。在所有患者中获得临床数据和DNA检测。采用Kaplan-Meier法绘制生存曲线，各组间比较采用log-rank检验。结果：共纳入108例无血缘关系的疑似HoFH先证者，平均年龄14.9岁。三种最常见的变体是W 483 X（c.1448 G > A）、A627 T（c.1879 G > A）、H583 Y（c.1747 C > T）。混合杂合子占64.8%（70例），真性HoFH占21.3%（23例）。真正的HoFH显示出更高的LDL-C水平相比，化合物HoFH（16.8？？3.6 mmol/L vs. 15.0 +/- 3.1 mmol/L，P = 0.022）。在随访期间，只有21.2%的患者表现出LDL-C降低超过50%。Kaplan-Meier分析显示，与其他基因型先证者相比，真正的HoFH先证者的生存率显著更差（13年生存率;分别为20.3%和76.7%; P = 0.016）。此外，真正的HoFH显示，2.8倍（P = 0.022）增加任何死亡和3.0倍（P = 0.023）增加心血管死亡风险相对于其他FH.Conclusions：本报告显示，HoFH具有毁灭性的后果，患者往往只有在他们已经暴露于严重升高的LDL-C多年后才被诊断。系统筛查和早期强化治疗是这些年轻HoFH患者的绝对要求。(C)2022年国家脂质协会。爱思唯尔公司出版All rights reserved.
Background: There is a lack of large-scale data on the clinical and genotype characteristics of homozygous familial hypercholesterolemia (HoFH) patients in Asia.Objective: To define the characteristics of phenotypic and genetic HoFH probands from mainland China.Methods: We collected data from patients with suspected HoFH from ten clinical hospitals across mainland China from 2003 to 2019. Clinical data and DNA testing were obtained in all patients. The Kaplan-Meier method was used to generate survival curves, and the groups were compared with the log-rank test.Results: A total of 108 unrelated probands with suspected HoFH (mean age 14.9 years) were included. The three most common variants were W483X (c.1448 G > A), A627T (c.1879 G > A), H583Y (c.1747 C > T). The majority (64.8%) were compound heterozygotes (n = 70), 23 (21.3%) were true HoFH patients. True HoFH showed higher LDL-C levels compared to compound HoFH (16.8 ??3.6 mmol/L vs. 15.0 +/- 3.1 mmol/L, P = 0.022). During follow-up, only 21.2% patients exhibited an LDL-C reduction of more than 50%. Kaplan-Meier analysis showed that the true HoFH probands had significantly worse survival rates compared to other genotype probands (13-year survival; 20.3% vs. 76.7%, respectively; P = 0.016). In addition, true HoFH shows that 2.8-fold (P = 0.022) increase any death and 3.0-fold (P = 0.023) increase cardiovascular death risk in relative to other FH.Conclusions: This report shows that HoFH has devastating consequences, and that patients are often only diagnosed after they have been exposed to severely elevated LDL-C for years. Systematic screening and early intensive treatment are an absolute requirement for these young individuals with HoFH. (C) 2022 National Lipid Association. Published by Elsevier Inc. All rights reserved.