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. Methods and 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 C3T 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 approximate to 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.