机构：[1]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, Beijing 100037, China.[2]Department of Cardiology, Peking University People’s Hospital, Beijing 100044, China.[3]Department of Cardiology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.心脏科（内科专业）首都医科大学宣武医院[4]Guangdong Cardiovascular Institute, Guangdong Provincial Key Laboratory of Clinical Pharmacology, Guangzhou 510080, China.[5]Department of Cardiology, Gansu Provincial People’s Hospital, Lanzhou 730000, Gansu, China.
BackgroundAlthough 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.MethodsA 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.ResultsOverall, 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.ConclusionsThe 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.
基金：
This work was supported by the Capital Health Development Fund (201614035),and CAMS Major Collaborative Innovation Project (2016-I2M-1-011) awarded to Dr.Jian-Jun Li, MD, PhD.
第一作者机构：[1]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, Beijing 100037, China.
通讯作者：
通讯机构：[1]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, Beijing 100037, China.
推荐引用方式(GB/T 7714)：
Di Sun,Bing-Yang Zhou,Sha Li,et al.Genetic basis of index patients with familial hypercholesterolemia in Chinese population: mutation spectrum and genotype-phenotype correlation[J].LIPIDS IN HEALTH AND DISEASE.2018,17(1):252.doi:10.1186/s12944-018-0900-8.
APA：
Di Sun,Bing-Yang Zhou,Sha Li,Ning-Ling Sun,Qi Hua...&Jian-Jun Li.(2018).Genetic basis of index patients with familial hypercholesterolemia in Chinese population: mutation spectrum and genotype-phenotype correlation.LIPIDS IN HEALTH AND DISEASE,17,(1)
MLA：
Di Sun,et al."Genetic basis of index patients with familial hypercholesterolemia in Chinese population: mutation spectrum and genotype-phenotype correlation".LIPIDS IN HEALTH AND DISEASE 17..1(2018):252
