GENETIC RESEARCHES AMONG MALAYSIAN FAMILIAL HYPERCHOLESTEROLAEMIC POPULATION

Abstract

ABSTRACT Background: Familial hypercholesterolaemia (FH) is one of the most frequent inherited metabolic disorders that can lead to a risk of premature cardiovascular disease. Publications on FH are mainly from western patients as there is little research on Asians, including Malaysians. The aim of this review is to provide an up-to- date information on Malaysian studies on FH genotyping and its relation to the phenotype of the affected patients. Method: A search was conducted for data from online databases on FH in Malaysia. Results: The mutation spectrum for FH among Malaysian patients was extremely broad. The gene variants were located mainly in the low-density lipoprotein receptor (LDLR) and apolipoprotein B-100 (APOB-100) genes rather than in the proprotein convertase subtilisin kexin type 9 (PCSK9) gene. The exon 9 and 14 were the hotspots in the LDLR gene. The most frequent mutation was p.Cys255Ser, at 12.5%, followed by p.Arg471Gly, at 11%, and the most common single nucleotide polymorphism (SNP) was c.1060+7 T>C at 11.7%. The LDLR gene variants were more common compared to the APOB-100 gene variants, while variants in the PCSK9 gene were very few. Phenotype-genotype associations were identified. Subjects with LDLR and APOB-100 genes mutations had a higher frequency of cardiovascular disease, a family history of hyperlipidaemia and tendon xanthoma and a higher low-density lipoprotein cholesterol (LDL-C) level than non-carriers. Conclusion: Research on Malaysian familial hypercholesterolaemic patients by individual groups is encouraging. However, more extensive molecular studies on FH on a national scale, with a screening of the disease-causing mutations together with a comprehensive genotype-phenotype association study, can lead to a better outcome for patients with the disease.