Association of polymorphisms at the SR-BI gene locus with plasma lipid levels and body mass index in a white population

The scavenger receptor class B type I (SR-BI) is a lipoprotein receptor tha t has been shown to be important in high density lipoprotein cholesterol (H DL-C) metabolism in mice. To determine its role in humans, we have characte rized the human SR-BI gene and investigated its genetic variation in 489 wh ite men and women. Five variants were demonstrated: 2 in introns (3 and 5) and 3 in exons (1, 8, and ii). Three variants at exons 1 and 8 and intron 5 with allele frequencies >0.1 were used to examine associations with lipid or anthropometric variables. The exon 1 variant was significantly (P<0.05) associated with increased HDL-C and lower low density lipoprotein cholester ol (LDL-C) values in men, but no associations were observed in women. The e xon 8 variant was associated in women with lower LDL-C concentrations (3.05 +/-0.98 mmol/L and 3.00+/-0.93 mmol/L for heterozygotes and homozygotes, re spectively) compared with women homozygous for the common allele (3.39+/-1. 09 mmol/L, P=0.043). No associations for this variant were observed in men. Women carriers of the intron 5 variant showed a higher body mass index (23 .8+/-3.8 kg/m(2), P=0.031) than those women homozygous for the common allel e (22.4+/-3.4 kg/m(2)). Similar results were observed after haplotype analy sis. Multiple regression analysis using HDL-C, LDL-C, and body mass index a s dependent variables and age, sex, and each of the genetic variants as pre dictors also provided similar results. The associations found with both LDL -C and HDL-C suggest that SR-BI may play a role in the metabolism of both l ipoprotein classes in humans.