Homozygous familial hypercholesterolemia in China: Genetic and clinical characteristics from a real-world, multi-center, cohort study

Long Jiang, Robert M. Stoekenbroek, Feng Zhang, Qian Wang, Wei Yu, Hui Yuan, Gaojun Cai, Yunqin Chen, Guoping Li, Yanling Yang, Yanan Zhang, Xiaoshu Cheng, Handong Zhu, Hongwen Zhou, Ping Ye, Shengkai Yan, Xu Wang, Wenfeng Wu, Rongjuan Li, Jinjie XieJian Jiao, Shitong Cheng, Wenquan Niu, Juan Chen, Shiwei Yang, Yujie Zhou, John J. P. Kastelein, Ya Yang, Luya Wang

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5 Citations (Scopus)


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.
Original languageEnglish
Pages (from-to)306-314
Number of pages9
JournalJournal of clinical lipidology
Issue number3
Early online date2022
Publication statusPublished - 1 May 2022


  • Diagnosis
  • Familial Hypercholesterolaemia
  • Homozygous
  • Lipid-lowering Therapy
  • Phenotype

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