title: Association between a novel 11-base pair deletion mutation in the promoter region of the scavenger receptor class B type I gene and plasma HDL cholesterol levels in Taiwanese Chinese.
abstract: OBJECTIVE
  Scavenger receptor class B type I (SR-BI) is a multiligand cell-surface receptor that mediates the selective uptake of lipid from HDL cholesterol (HDL-C) into cells. This study hypothesized an association between functional variants in the promoter region of SR-BI gene and HDL-C levels.
  
  
  RESULTS
  We identified 2 novel mutations in the SR-BI gene promoter region by using single-strand conformation polymorphism. One mutation was an 11-bp CCCCGCCCCGT deletion mutation from positions -140 to -150 relative to the transcription start site, corresponding to an Sp1 binding site; the other was a C-->T substitution at position -142. Twenty-six of 690 unrelated subjects were heterozygous for the -140 to -150 deletion mutation, and the allele frequency in this population was 0.02. This study showed that the deletion variant prevented binding of Sp1 to this region of the SR-BI promoter and effectively reduced transcriptional activities in HepG2 cells. Notably, the -140 to -150 deletion mutation was significantly associated with increased HDL-C levels and explained approximately 0.5% of the variation in HDL-C levels in this population.
  
  
  CONCLUSIONS
  A genetic variant at the SR-BI gene promoter region might explain a significant proportion of individual differences in HDL-C levels among Taiwanese Chinese. Our results require further replication in an independent population.
authors.affiliation: First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Lung-An
authors.initials: LA
authors.lastname: Hsu
authors.forename: Yu-Lin
authors.initials: YL
authors.lastname: Ko
authors.forename: Semon
authors.initials: S
authors.lastname: Wu
authors.forename: Ming-Sheng
authors.initials: MS
authors.lastname: Teng
authors.forename: Tsui-Yi
authors.initials: TY
authors.lastname: Peng
authors.forename: Chun-Fei
authors.initials: CF
authors.lastname: Chen
authors.forename: Chin-Fen
authors.initials: CF
authors.lastname: Chen
authors.forename: Ying-Shiung
authors.initials: YS
authors.lastname: Lee
mesh_terms: D044466:Asian People / Q000235:genetics; D020029:Base Pairing; D001483:Base Sequence; D018955:CD36 Antigens / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood*; D004252:DNA Mutational Analysis; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000208:ethnology / Q000235:genetics; D016014:Linear Models; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic / Q000235:genetics; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D017384:Sequence Deletion; D013624:Taiwan
chemical_list: D018955:CD36 Antigens; D008076:Cholesterol, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C495124:SCARB1 protein, human; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B