Association of the Sst-I polymorphism at the APOC3 gene locus with variations in lipid levels, lipoprotein subclass profiles and coronary heart disease risk: the Framingham offspring study

Apolipoprotein (apo) CIII participates in the regulation of the metabolism of triglyceride-rich lipoproteins and it is a major component of chylomicro ns and VLDL. The APOC3 gene is on chromosome 11q23 and is highly polymorphi c. The less common allele (S2) of the SstI polymorphism on the 3' untransla ted region of the APOC3 gene has been previously associated with increased triglycerides, total cholesterol (TC), and apoCIII levels and cardiovascula r risk on several, but not all, studies. The aim of this study was to exami ne the association of this polymorphism with plasma lipid levels, lipoprote in subfractions and coronary heart disease (CHD) risk in a population-based study: The Framingham Offspring Study. The frequency of the S2 allele was 0.086, consistent with previous reports in Caucasian populations. In men, t he S2 allele was associated with lower concentrations of high-density lipop rotein cholesterol (HDL-C; P < 0.04) and HDL2-C (P < 0.02) and a significan t increase in apoCIII non-HDL (P < 0.05). TG levels were higher in men carr iers of the S2 allele, but this association did not reach statistical signi ficance (P = 0.30). Conversely, in women, the S2 allele was associated with increased TC (P < 0.03), low-density lipoprotein cholesterol (LDL-C; P < 0 .03), and ApoB levels (P < 0.04). Lipoproteins subfractions were also exami ned using nuclear magnetic resonance (NMR) spectroscopy. S2 male carriers h ad significantly lower concentrations of large LDL and a significant reduct ion in LDL particle size (P < 0.04). In women, there was a significant incr ease in intermediate LDL particles (P < 0.05) with no significant effect on lipoprotein diameters. We also examined the associations between the S2 al lele and biochemical markers of glucose metabolism. In men, the S2 allele w as associated with elevated fasting insulin concentrations (P < 0.04), wher eas no significant associations were observed in women. Despite the describ ed associations with lipid and glucose metabolism related risk factors, we did not find any significant increase in CHD risk associated with the S2 al lele in this population. ((C) 2001 Elsevier Science Ireland Ltd. All rights reserved.