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Genetic Variation at the Scavenger Receptor Class B Type I Gene Locus Determines Plasma Lipoprotein Concentrations and Particle Size and Interacts with Type 2 Diabetes: The Framingham Study

Nutrition and Genomics Laboratory (D.O., D.C., O.C., J.M.O.) and Lipid Metabolism Laboratory (E.J.S.), Jean Mayer–U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts 02111; Boston University School of Public Health (S.D., L.A.C.) and Boston University School of Medicine (P.W.F.W.), Boston, Massachusetts 02118; Framingham Heart Study (P.W.F.W.), Framingham, Massachusetts 01702; and General Internal Medicine Department (J.B.M.), Massachusetts General Hospital, Boston, Massachusetts 02114

Address all correspondence and requests for reprints to: Dr. J. M. Ordovas, Nutrition and Genomics Laboratory, Jean Mayer–U.S. Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, Massachusetts 02111. E-mail: jose.ordovas{at}tufts.edu.

The scavenger receptor class B type I (SR-BI) is a key component in the reverse cholesterol transport pathway. We have previously reported three common polymorphisms associated with plasma lipids and body mass index. We hypothesized that diabetic status may interact with these polymorphisms in determining plasma lipid concentrations and particle size. We evaluated this hypothesis in 2463 nondiabetic (49% men) and 187 diabetic (64% men) participants in the Framingham Study. SR-BI and APOE genotypes, anthropometric, clinical, biochemical, and lifestyle variables were determined. After multivariate adjustment, we found a consistent association between the exon 8 polymorphism and high-density lipoprotein cholesterol concentration and particle size. Interaction effects were not significant for exon 8 and intron 5 polymorphisms. However, we found statistically significant interactions between SR-BI exon 1 genotypes and type 2 diabetes, indicating that diabetic subjects with the less common allele (allele A) have lower lipid concentrations. For low-density lipoprotein cholesterol, the adjusted means (±SE) were 3.31 ± 0.03 and 3.29 ± 0.04 mmol/liter for G/G and G/A or A/A in nondiabetics, respectively, compared with 3.19 ± 0.10 and 2.75 ± 0.01 mmol/liter for G/G and G/A or A/A in diabetics (P = 0.03 for interaction). Similar results were obtained for HDL₂-C. In conclusion, SR-BI gene variation modulates the lipid profile, particularly in type 2 diabetes, contributing to the metabolic abnormalities in these subjects.

This work was supported by National Institutes of Health/National Heart, Lung and Blood Institute (NIH/NHLBI) Grant HL54776, NIH/NHLBI contract no. 1-38038; contracts 53-K06-5-10 and 58-1950-9-001 from the U.S. Department of Agriculture Research Service; and Grants PR2002-0115 (to D.C., University of Valencia) and PR2002-0116 (to O.C., Jaume I University) from the Ministerio de Educación y Cultura, Spain.

Abbreviations: apo, Apolipoprotein; BMI, body mass index; CI, confidence interval(s); GLM, general linear model; HDL, high-density lipoprotein; HDL-C, HDL-cholesterol; LDL, low-density lipoprotein; LDL-C, LDL-cholesterol; SNP, single nucleotide polymorphism; SR-BI, scavenger receptor class B type I.

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