Genetic basis of index patients with familial hypercholesterolemia in Chinese population: mutation spectrum and genotype-phenotype correlation

Lipids in Health and Disease

Yun-Shan Cao¹  Ning-Ling Sun²  Qi Hua³  Bing-Yang Zhou⁴  Di Sun⁴  Yuan-Lin Guo⁴  Jian-Jun Li⁴  Geng Liu⁴  Sha Li⁴  Cheng-Gang Zhu⁴  Na-Qiong Wu⁴  Ying Gao⁴  Chuan-Jue Cui⁴  Shu-Lin Wu⁵ 

[1] Department of Cardiology, Gansu Provincial People’s Hospital;Department of Cardiology, Peking University People’s Hospital;Department of Cardiology, Xuanwu Hospital, Capital Medical University;Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College;Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology;

关键词: Familial hypercholesterolemia;    Lipid;    LDLR;    APOB;    PCSK9;   

DOI  :  10.1186/s12944-018-0900-8

来源: DOAJ

【 摘 要 】

Abstract Background Although there have been many reports in the genetics of familial hypercholesterolemia (FH) worldwide, studies in regard of Chinese population are lacking. In this multi-center study, we aim to characterize the genetic spectrum of FH in Chinese population, and examine the genotype-phenotype correlations in detail. Methods A total of 285 unrelated index cases from China with clinical FH were consecutively recruited. Next-generation sequencing and bioinformatics tools were used for mutation detection of LDLR, APOB and PCSK9 genes and genetic analysis. Results Overall, the detection rate is 51.9% (148/285) in the unrelated index cases with a total of 119 risk variants identified including 84 in the LDLR gene, 31 in APOB and 4 in PCSK9 gene. Twenty-eight variants were found in more than one individual and LDLR c.1448G > A (p. W483X) was most frequent one detected in 9 patients. Besides, we found 8 (7 LDLR and 1 APOB) novel variants referred as “pathogenic (or likely pathogenic) variants” according to in silico analysis. In the phenotype analysis, patients with LDLR null mutation had significantly higher LDL cholesterol level than LDLR defective and APOB/PCSK9 mutation carriers and those with no mutations (p < 0.001). Furthermore, 13 double heterozygotes, 16 compound heterozygotes and 5 true LDLR homozygotes were identified and the true LDLR homozygotes had the most severe phenotypes. Conclusions The present study confirmed the heterogeneity of FH genetics in the largest Chinese cohort, which could replenish the knowledge of mutation spectrum and contribute to early screening and disease management.

【 授权许可】

Unknown