LDLR and ApoB are major genetic causes of autosomal dominant hypercholesterolemia in a taiwanese population
Journal
Journal of the Formosan Medical Association
Journal Volume
106
Journal Issue
10
Pages
799-807
Date Issued
2007
Author(s)
Abstract
Background/Purpose: Autosomal dominant hypercholesterolemia (ADH) is an autosomal dominant inherited disease characterized by an increase in low-density lipoprotein cholesterol levels and premature coronary heart disease, which can be caused by mutations in genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9). There is scant information with regard to the role played by each gene in the Taiwanese ADH population, especially the newly discovered PCSK9 gene. Methods: We used coupling heteroduplex analysis based on a denaturing high performance liquid chromatography system and DNA sequencing to screen for the LDLR gene, APOB gene and PCSK9 gene in 87 ADH cases recruited from 30 unrelated Taiwanese families. Results: We did not find any mutation-causing variant of the PCSK9 gene in our cases and thus excluded PCSK9 as the major culprit mutation in these families. On the other hand, we identified six previously reported LDLR gene mutations (C107Y, D69N, R385W, W462X, G170X, V408M), two novel LDLR gene mutations (FsG631 and splice junction mutation of intron 10), and one known mutation (R3500W) and one novel missense mutation (T3540M) in the APOB gene that were present in 55 members from 18 ADH families (60%). R3500W, rather than R3500Q, could be the principle mutation responsible for familial defective apolipoptotein B in Taiwanese. Conclusion: The results of our study reveal a characteristic mutation pattern of ADH in Taiwan, mainly in the LDLR and APOB genes. However, PCSK9 gene mutation may not be a major cause of ADH in our study population. ?2007 Elsevier & Formosan Medical Association.
SDGs
Other Subjects
apolipoprotein B; arginine; asparagine; aspartic acid; cysteine; glycine; kexin; lipid; low density lipoprotein receptor; methionine; serine proteinase; subtilisin; tryptophan; tyrosine; valine; adolescent; adult; aged; amino acid substitution; article; autosomal dominant disorder; controlled study; denaturing high performance liquid chromatography; DNA sequence; family; female; gene function; genetic analysis; human; hypercholesterolemia; intron; major clinical study; male; missense mutation; polymerase chain reaction; Taiwan
Type
journal article