Proprotein-Convertase Subtilisin-Kexin Type 9 and Low-Density Lipoprotein Receptor Genotype Distribution and Statin Association in Filipino American Women

Filipino American women (FAW) have high incidence of coronary heart disease and high low-density lipoprotein cholesterol (LDL-C). The distribution of rs11206510 proprotein-convertase subtilisin-kexin type 9 (PCSK9) and rs1122608 low-density lipoprotein receptor (LDLR) single nucleotide polymorphisms (SNPs), known for genetic influences on LDL-C, is unknown in this population. The objective of this study was to examine the genetic determinants of LDL-C, their association with LDL-C, and effects of statins on LDL-C given the genetic determinants in this high-risk population. Data were obtained from the FAW Cardiovascular Study ( N = 338) of women ages 40 to 65 years from four major U.S. cities between 2011 and 2013. Roche Modular methodology and Luminex-oligonucleotide ligation assay procedure were used for allele frequency, genotype, LDL-C, and lipid analysis. Analysis of variance was used to determine differences between genotype groups. Genotype and statin effect on LDL-C were tested using the generalized linear model procedure of SAS. The distribution of rs11206510 PCSK9 genotypes was 88% TT, 11% TC, and 1% CC, and the rs1122608 LDLR genotype distribution was 83% GG, 17% GT, and 0% TT. These SNPs showed no association with mean LDL-C in this cohort. FAW on statin medications had lower LDL levels regardless of their PCSK9 or LDLR genotypes. Most FAW had a gain-of-function allele of PCSK9 and LDLR. This predominance in FAW cohort may account for the high percentage of subjects with elevated LDL-C. In a population at high risk for hypercholesterolemia, optimal treatment with statins should be considered where appropriate