© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Association of Polymorphisms at the SR-BI Gene Locus With Plasma Lipid Levels and Body Mass Index in a White Population
From Millennium Pharmaceuticals, Inc, Cambridge, Mass (S.A., M.D., J.K., S.S., E.A.W.); the Jean Mayer–US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (D.O., D.C., J.M.O.); and the Department of Biochemistry and Molecular and Cellular Biology, University of Zaragoza, Zaragoza, Spain (M.P., A.C., P.M.).
Correspondence to Jose M. Ordovas, Jean Mayer–US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111. E-mail ordovas_li{at}hnrc.tufts.edu
Abstract—The scavenger receptor class B type I (SR-BI) is a lipoprotein receptor that has been shown to be important in high density lipoprotein cholesterol (HDL-C) metabolism in mice. To determine its role in humans, we have characterized the human SR-BI gene and investigated its genetic variation in 489 white men and women. Five variants were demonstrated: 2 in introns (3 and 5) and 3 in exons (1, 8, and 11). 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 cholesterol (LDL-C) values in men, but no associations were observed in women. The exon 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, respectively) 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/m2, P=0.031) than those women homozygous for the common allele (22.4±3.4 kg/m2). Similar results were observed after haplotype analysis. Multiple regression analysis using HDL-C, LDL-C, and body mass index as dependent variables and age, sex, and each of the genetic variants as predictors 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 lipoprotein classes in humans.
Key Words: scavenger receptor class B type I • single-nucleotide polymorphism • body mass index • LDL cholesterol • HDL cholesterol
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