Scavenger receptor class B type I protein as an independent predictor of high-density lipoprotein cholesterol levels in subjects with hyperalphalipoproteinemia.

CONTEXT In mice, scavenger receptor class B, type I (SR-BI) receptor protein deficiency is associated with elevated high-density lipoprotein (HDL)-cholesterol (HDL-C) levels. OBJECTIVE Our objective was to determine the relationship between SR-BI protein and HDL-C levels in humans. DESIGN This was a prospective study of adults with hyperalphalipoproteinemia. Fasting blood was obtained for lipid and lipoprotein measurement, genomic DNA, and monocyte-derived macrophages. SR-BI protein levels were measured by Western blots, and SR-BI activity was measured by cholesteryl ester (CE) uptake of each donor's radiolabeled HDL with their monocyte-derived macrophages, or by degradation and specific cell association of dual-labeled HDL in vitro. SETTING The study was performed in a tertiary university teaching hospital. RESULTS The mean age was 57.2 +/- 10.9 yr (n = 65). SR-BI protein levels were inversely associated with HDL-C levels (P < 0.002), HDL particle size (P < 0.05), and positively associated with CE uptake (P < 0.004); there was no association with plasma apolipoprotein levels. SR-BI protein levels (P = 0.01) were independent predictors of HDL-C levels. Subjects who were carriers of the A allele for the rs4238001 (glycine to serine at position 2) polymorphism [single nucleotide polymorphism (SNP)] had lower SR-BI protein levels (P = 0.01), whereas carriers of the C allele for the rs2278986 SNP also had lower SR-BI protein levels (P = 0.02). Body mass index (P = 0.05), rs4238001 (P = 0.01), and rs2278986 (P = 0.01) SNPs were independent predictors of SR-BI protein levels. In vitro studies of murine macrophages stably expressing the glycine to serine at position 2 SNP showed less degradation (P < 0.0004) and specific cell association (P < 0.0004) of [(125)I, (3)H]-CE-labeled HDL. CONCLUSIONS SR-BI protein has an independent effect on HDL-C levels in women with hyperalphalipoproteinemia. Two SNPs were significantly associated with lower SR-BI protein levels.