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.
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.
Hsu
Lung-An
LA
First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
Ko
Yu-Lin
YL
Wu
Semon
S
Teng
Ming-Sheng
MS
Peng
Tsui-Yi
TY
Chen
Chun-Fei
CF
Chen
Chin-Fen
CF
Lee
Ying-Shiung
YS
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
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