title: Genetic contribution of SCARB1 variants to lipid traits in African Blacks: a candidate gene association study.
abstract: BACKGROUND
  High-density lipoprotein cholesterol (HDL-C) exerts many anti-atherogenic properties including its role in reverse cholesterol transport (RCT). Scavenger receptor class B member 1 (SCARB1) plays a key role in RCT by selective uptake of HDL cholesteryl esters. We aimed to explore the genetic contribution of SCARB1 to affecting lipid levels in African Blacks from Nigeria.
  
  
  METHODS
  We resequenced 13 exons and exon-intron boundaries of SCARB1 in 95 individuals with extreme HDL-C levels using Sanger method. Then, we genotyped 147 selected variants (78 sequence variants, 69 HapMap tagSNPs, and 2 previously reported relevant variants) in the entire sample of 788 African Blacks using either the iPLEX Gold or TaqMan methods. A total of 137 successfully genotyped variants were further evaluated for association with major lipid traits.
  
  
  RESULTS
  The initial gene-based analysis demonstrated evidence of association with HDL-C and apolipoprotein A-I (ApoA-I). The follow-up single-site analysis revealed nominal evidence of novel associations of nine common variants with HDL-C and/or ApoA-I (P < 0.05). The strongest association was between rs11057851 and HDL-C (P = 0.0043), which remained significant after controlling for multiple testing using false discovery rate. Rare variant association testing revealed a group of 23 rare variants (frequencies ≤ 1%) associated with HDL-C (P = 0.0478). Haplotype analysis identified four SCARB1 regions associated with HDL-C (global P < 0.05).
  
  
  CONCLUSIONS
  To our knowledge, this is the first report of a comprehensive association study of SCARB1 variations with lipid traits in an African Black population. Our results showed the consistent association of SCARB1 variants with HDL-C across various association analyses, supporting the role of SCARB1 in lipoprotein-lipid regulatory mechanism.
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, 15261, USA. vin4@pitt.edu.
authors.forename: Vipavee
authors.initials: V
authors.lastname: Niemsiri
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, 15261, USA. xbw1@pitt.edu.
authors.forename: Xingbin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, 15261, USA. dip16@pitt.edu.
authors.forename: Dilek
authors.initials: D
authors.lastname: Pirim
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, 15261, USA. zhr2@pitt.edu.
authors.forename: Zaheda H
authors.initials: ZH
authors.lastname: Radwan
authors.affiliation: Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, 15261, USA. bunkerc@pitt.edu.
authors.forename: Clareann H
authors.initials: CH
authors.lastname: Bunker
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, 15261, USA. barmada@pitt.edu.
authors.forename: M Michael
authors.initials: MM
authors.lastname: Barmada
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, 15261, USA. kamboh@pitt.edu.
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
authors.affiliation: Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto Street, Pittsburgh, PA, 15261, USA. fyd1@pitt.edu.
authors.forename: F Yesim
authors.initials: FY
authors.lastname: Demirci
mesh_terms: D000328:Adult; D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood; D044383:Black People / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000379:methods*; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016014:Linear Models; D008055:Lipids / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009549:Nigeria; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D051122:Scavenger Receptors, Class B / Q000235:genetics*; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008055:Lipids; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B