Polymorphisms at the SRBI locus are associated with lipoprotein levels in subjects with heterozygous familial hypercholesterolemia.

Scavenger receptor, class B, type 1 (SRBI) is a promising candidate gene involved in the pathophysiology of atherosclerosis. We have examined the association of three common polymorphisms at the SRBI locus in 77 subjects who were heterozygous for familial hypercholesterolemia (FH). The alleles represented by polymorphisms in exon 1 and exon 8 were associated with variation in plasma concentrations of fasting triglyceride (TG). Mean plasma TG concentrations for homozygotes for the most common allele, and for heterozygotes and homozygotes for the less common allele were 85 +/- 6, 111 +/- 9 and 135 +/- 22 mg/dl (p = 0.011) for exon 1, and 96 +/- 11, 86 +/- 6 and 134 +/- 13 mg/dl (p = 0.007) for exon 8, after adjustment for age, sex and body mass index. In addition, the exon 8 polymorphism was associated with increased total cholesterol (320 +/- 15, 340 +/- 8 and 388 +/- 18 mg/dl, p = 0.015), very low density lipoprotein (VLDL) cholesterol (18 +/- 2.9, 15.7 +/- 1.6 and 33.4 +/- 3.9 mg/dl, p < 0.001) and low density lipoprotein (LDL) cholesterol (251 +/- 15, 270 +/- 8 and 312 +/- 10 mg/dl, p = 0.041) concentrations. In agreement with animal studies, our data also suggest a role for the SRBI in the metabolism of apolipoprotein B (apoB)-containing lipoproteins in humans. This pathway may constitute a backup mechanism to LDL receptor-mediated pathways for the catabolism of these lipoproteins, which could be particularly relevant in subjects with high levels of apoB-containing lipoproteins, such as those occurring in patients with FH.