Genetic polymorphisms in LDLR, APOB, PCSK9 and other lipid related genes associated with familial hypercholesterolemia in Malaysia

• Published in: PloS one Vol. 8; no. 4; p. e60729
• Main Authors: Lye, Say-Hean, Chahil, Jagdish Kaur, Bagali, Pramod, Alex, Livy, Vadivelu, Jamunarani, Ahmad, Wan Azman Wan, Chan, Siew-Pheng, Thong, Meow-Keong, Zain, Shamsul Mohd, Mohamed, Rosmawati
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.04.2013; Public Library of Science (PLoS)
• Subjects: Adult; APOB gene; Apolipoprotein B; Apolipoproteins; Apolipoproteins B - genetics; Atherosclerosis; Biology; Cardiovascular disease; Cardiovascular diseases; Cholesterol; Cohort Studies; Deoxyribonucleic acid; Disease control; DNA; DNA microarrays; Family medical history; Female; Gene Frequency; Genes; Genetic aspects; Genetic diversity; Genetic testing; Genetic variance; Genotype; Genotyping; Growth hormones; Health risks; Heart diseases; Hereditary diseases; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II - genetics; Hyperlipoproteinemia Type II - metabolism; Hyperlipoproteinemia Type II - pathology; Kexin; LDLR gene; Lipid Metabolism - genetics; Lipids; Lipoprotein (low density) receptors; Low density lipoprotein receptors; Low density lipoproteins; Malaysia; Male; Medicine; Metabolism; Middle Aged; Mines; Mutation; Polymorphism, Single Nucleotide; Proprotein Convertase 9; Proprotein convertases; Proprotein Convertases - genetics; Receptor density; Receptors, LDL - genetics; Risk; Risk management; Serine Endopeptidases - genetics; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Studies; Subtilisin; Kuala Lumpur Malaysia; Selangor Malaysia; Malaysia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0060729

Familial hypercholesterolemia (FH) is an autosomal dominant disorder characterized by elevations in total cholesterol (TC) and low density lipoprotein cholesterol (LDLc). Development of FH can result in the increase of risk for premature cardiovascular diseases (CVD). FH is primarily caused by genetic variations in Low Density Lipoprotein Receptor (LDLR), Apolipoprotein B (APOB) or Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) genes. Although FH has been extensively studied in the Caucasian population, there are limited reports of FH mutations in the Asian population. We investigated the association of previously reported genetic variants that are involved in lipid regulation in our study cohort. A total of 1536 polymorphisms previously implicated in FH were evaluated in 141 consecutive patients with clinical FH (defined by the Dutch Lipid Clinic Network criteria) and 111 unrelated control subjects without FH using high throughput microarray genotyping platform. Fourteen Single Nucleotide Polymorphisms (SNPs) were found to be significantly associated with FH, eleven with increased FH risk and three with decreased FH risk. Of the eleven SNPs associated with an increased risk of FH, only one SNP was found in the LDLR gene, seven in the APOB gene and three in the PCSK9 gene. SNP rs12720762 in APOB gene is associated with the highest risk of FH (odds ratio 14.78, p<0.001). Amongst the FH cases, 108 out of 141 (76.60%) have had at least one significant risk-associated SNP. Our study adds new information and knowledge on the genetic polymorphisms amongst Asians with FH, which may serve as potential markers in risk prediction and disease management.