Abstract
Background: Autosomal dominant hypercholesterolaemia (ADH) is a genetic disorder that is mainly resulted from defects in the low-density lipoprotein receptor (LDLR) and apolipoprotein B-100(APOB-100) genes. Few studies of familial hypercholesterolaemia (FH) have been conducted in Malaysia, that makes the underlying main defect remains not well understood.Objectives: This study was aimed to describe the molecular aspects of FH among Malaysian subjects.Methods and Findings: We studied a group of 74 familial hypercholesterolaemic patients and 77 healthy control subjects. The promoter region and the 18 exons of the low-density lipoprotein receptor gene were screened by denaturing high-performance liquid chromatography (DHPLC) to detect small deletions, insertions  and nucleotide substitutions, while DNA sequencing was applied to look for gene variants in amplicons  of exon 26 and 29 in the APOB -100 gene. A total of five gene sequence variants in the LDLR gene were reported in 54.1% of the studied patients. P.Arg471Arg variant has the highest frequency of 20.3% among the study subjects. One intronic mutation (c.313+1G>A) and one missense mutation (p.Arg 385Try) were found to be pathogenic, while the other three variants were reported to be non-pathogenic by the in silico analyses. Nine variants were reported in the APOB-100 gene among familial hypercholesterolaemic patients with a non-significant difference in their frequency from the control subjects.Conclusions: five LDLR gene sequence variants were reported. However, nine polymorphisms were stated in the APOB -100 gene. However they were not associated with FH phenotype among this cohort. These findings suggested that LDLR gene mutation is the major genetic cause for FH among Malaysians. The results offer information on the genetic spectrum of FH among Malaysian cohort which can serve as a platform for further genetic studies.
Highlights
Familial hypercholesterolaemia (FH), (OMIM143890) is the first genetic disorder of lipid metabolism that is characterized both clinically and molecularly [1]
Nine polymorphisms were stated in the APOB-100 gene
These findings suggested that lowdensity lipoprotein receptor (LDLR) gene mutation is the major genetic cause for familial hypercholesterolaemia (FH) among Malaysians
Summary
Familial hypercholesterolaemia (FH), (OMIM143890) is the first genetic disorder of lipid metabolism that is characterized both clinically and molecularly [1]. It is transmitted in an autosomal dominant manner [1]. Familial hypercholesterolaemia is characterized by elevated serum level of low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC), tendon xanthomas (TX) and early atherosclerosis, leading to premature atherosclerotic coronary artery disease (CAD) [2, 3]. Autosomal dominant hypercholesterolaemia (ADH) is a genetic disorder that is mainly resulted from defects in the lowdensity lipoprotein receptor (LDLR) and apolipoprotein B-100 (APOB100) genes. Few studies of familial hypercholesterolaemia (FH) have been conducted in Malaysia, that makes the underlying main defect remains not well understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
