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.
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.
Authors: Ruud Out; Menno Hoekstra; Saskia C A de Jager; Paula de Vos; Deneys R van der Westhuyzen; Nancy R Webb; Miranda Van Eck; Eric A L Biessen; Theo J C Van Berkel Journal: J Lipid Res Date: 2005-03-16 Impact factor: 5.922
Authors: Alfredo Morabia; Barbara M Ross; Michael C Costanza; Eftihia Cayanis; Maria Sol Flaherty; Gabriela B Alvin; Kamna Das; Richard James; An-Suei Yang; Oleg Evagrafov; T Conrad Gilliam Journal: Atherosclerosis Date: 2004-07 Impact factor: 5.162
Authors: Vipavee Niemsiri; Xingbin Wang; Dilek Pirim; Zaheda H Radwan; Clareann H Bunker; M Michael Barmada; M Ilyas Kamboh; F Yesim Demirci Journal: BMC Med Genet Date: 2015-11-12 Impact factor: 2.103