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

Autor: Yuan-Lin Guo, Sha Li, Bing-Yang Zhou, Shu-Lin Wu, Na-Qiong Wu, Ning-Ling Sun, Chuan-Jue Cui, Cheng-Gang Zhu, Ying Gao, Di Sun, Qi Hua, Yun-Shan Cao, Jian-Jun Li, Geng Liu
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Adult
Male
Apolipoprotein B
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Familial hypercholesterolemia
DNA Mutational Analysis
Hyperlipidemias
030204 cardiovascular system & hematology
Compound heterozygosity
Genetic analysis
PCSK9
03 medical and health sciences
0302 clinical medicine
Endocrinology
Asian People
medicine
Humans
Computer Simulation
lcsh:RC620-627
Genetic Association Studies
Genetics
biology
Research
Biochemistry (medical)
nutritional and metabolic diseases
Lipid
Middle Aged
medicine.disease
Null allele
lcsh:Nutritional diseases. Deficiency diseases
030104 developmental biology
LDLR
Receptors
LDL
Mutation (genetic algorithm)
LDL receptor
Apolipoprotein B-100
Mutation
biology.protein
lipids (amino acids
peptides
and proteins)
Female
APOB
Proprotein Convertase 9
Zdroj: Lipids in Health and Disease
Lipids in Health and Disease, Vol 17, Iss 1, Pp 1-8 (2018)
ISSN: 1476-511X
Popis: 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
Databáze: OpenAIRE
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