title: 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.
  
  
  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.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Vipavee
authors.initials: V
authors.lastname: Niemsiri
authors.forename: Xingbin
authors.initials: X
authors.lastname: Wang
authors.forename: Dilek
authors.initials: D
authors.lastname: Pirim
authors.forename: Zaheda H
authors.initials: ZH
authors.lastname: Radwan
authors.forename: John E
authors.initials: JE
authors.lastname: Hokanson
authors.forename: Richard F
authors.initials: RF
authors.lastname: Hamman
authors.forename: M Michael
authors.initials: MM
authors.lastname: Barmada
authors.forename: F Yesim
authors.initials: FY
authors.lastname: Demirci
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001055:Apolipoproteins B / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood*; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D051122:Scavenger Receptors, Class B / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D001055:Apolipoproteins B; D008076:Cholesterol, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B
keywords: SCARB1 protein, human; genetic association studies; genetic variation; haplotypes; lipids; polymorphism, genetic; sequence analysis, DNA