Impact of Genetic Variants in Human Scavenger Receptor Class B Type I ( SCARB1 ) on Plasma Lipid Traits

Abstract

Background— Scavenger receptor class B type 1 ( SCARB1 ) plays an important role in high-density lipoprotein cholesterol (HDL-C) metabolism in selective cholesteryl ester uptake and in free cholesterol cellular efflux. Methods and Results— This study aims to identify common (minor allele frequency ≥5%) and low-frequency/rare (minor allele frequency <5%) variants, using resequencing all 13 exons and exon-intron boundaries of SCARB1 in 95 individuals with extreme HDL-C levels selected from a population-based sample of 623 US non-Hispanic whites. The sequencing step identified 44 variants, of which 11 were novel with minor allele frequency <1%. Seventy-six variants (40 sequence variants, 32 common HapMap tag single nucleotide polymorphisms, and 4 relevant variants) were selected for genotyping in the total sample of 623 subjects followed by association analyses with lipid traits. Seven variants were nominally associated with apolipoprotein B (apoB; n=4) or HDL-C (n=3; P <0.05). Three variants associated with apoB remained significant after controlling false discovery rate. The most significant association was observed between rs4765615 and apoB ( P =0.0059), while rs11057844 showed the strongest association with HDL-C ( P =0.0035). A set of 17 rare variants (minor allele frequency ≤1%) showed significant association with apoB ( P =0.0284). Haplotype analysis revealed 4 regions significantly associated with either apoB or HDL-C. Conclusions— Our findings provide new information about the genetic role of SCARB1 in affecting plasma apoB levels in addition to its established role in HDL-C metabolism.