Human Molecular Genetics Advance Access published online on July 28, 2004
Human Molecular Genetics, doi:10.1093/hmg/ddh233
© 2004 by Oxford University Press
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1 Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA
* To whom correspondence should be addressed. E-mail: alessandro.doria{at}joslin.harvard.edu.
CD36 is a class B scavenger receptor recognizing a variety of ligands including long-chain fatty acids and modified LDL. We investigated whether genetic variability at this locus is a determinant of free fatty acids (FFA) plasma levels and risk of coronary artery disease in Caucasians. Typing of 21 polymorphic markers evenly spanning the CD36 gene revealed two linkage disequilibrium blocks that could be tagged by five polymorphisms (-33137A>G, -31118G>A, 25444G>A, 27645del>ins, and 30294G>C). In 585 non-diabetic individuals of Caucasian origin, the 30294G>C polymorphism was significantly associated with FFA levels (p=0.02) - an effect that was especially visible among men (p=0.009). A similar association was observed in this gender at -33137 (p=0.008) and -31118 (p=0.028). When the five tag polymorphisms were considered together, men carrying the AGGIG haplotype had 31% higher FFA (p=0.0002) and 20% higher triglycerides (p=0.025) than non-carriers. The same haplotype was associated with increased risk of coronary artery disease in 197 type 2 diabetic individuals from the US (OR=2.3, 95% CI 1.2-4.2). A similar tendency was observed in a group of 321 type 2 diabetic individuals from Italy (OR=1.4, 0.9-2.3), resulting in an overall relative risk of 1.6 (1.1-2.3, p=0.015) in the two populations considered together. By targeted resequencing, we identified a common variant in the CD36 promoter that is in strong linkage disequilibrium with the AGGIG haplotype and could be partly responsible for these findings. In conclusion, this comprehensive study of CD36 variability indicates that common polymorphisms at this locus modulate lipid metabolism and cardiovascular risk in Caucasians.
Article
A Common haplotype at the CD36 locus is associated with high free fatty acid levels and increased cardiovascular risk in caucasians
2 Endocrine Unit, Scientific Institute ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy
3 Department of Clinical and Experimental Medicine, University of Padova, Padova, Italy
4 Department of Medicine, Harvard Medical School, Boston, MA; Cardiology Division, Beth Israel Deaconess Medical Center, Boston, MA; Cardiology Associates, Anne Arundel Medical Center, Annapolis, MD
5 Department of Medicine, Harvard Medical School, Boston, MA; Cardiology Division, Beth Israel Deaconess Medical Center, Boston, MA
6 Department of Medicine, Harvard Medical School, Boston, MA; Heart and Vascular Center, Lahey Clinic, Burlington, MA
7 Department of Physiology and Biophysics, State University of New York, Stony Brook, NY
8 Endocrine Unit, Scientific Institute ‘Casa Sollievo della Sofferenza’, San Giovanni Rotondo, Italy; Department of Clinical Sciences, University ‘La Sapienza’, Rome, Italy
9 Research Division, Section on Genetics & Epidemiology, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, Boston, MA 02215; Department of Medicine, Harvard Medical School, Boston, MA
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