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


METHODS
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.


METHODS
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.
West
Michael
M
Department of Medicine, Division of Endocrinology and Metabolism, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
Greason
Erin
E
Kolmakova
Antonina
A
Jahangiri
Anisa
A
Asztalos
Bela
B
Pollin
Toni I
TI
Rodriguez
Annabelle
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D008076:Cholesterol, HDL / Q000097:blood*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D006801:Humans; D006951:Hyperlipoproteinemias / Q000097:blood* / Q000235:genetics; D008264:Macrophages / Q000201:enzymology; D008297:Male; D051379:Mice; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011446:Prospective Studies; D044469:Racial Groups / Q000235:genetics; D051122:Scavenger Receptors, Class B / Q000097:blood* / Q000172:deficiency* / Q000235:genetics; D055815:Young Adult
D008076:Cholesterol, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B