Delayed clearance of postprandial large TG-rich particles in normolipidemic carriers of LPL Asn291Ser gene variant

The carrier frequency of Asn291Ser polymorphism of the lipoprotein lipase ( LPL) gene is 4-6% in the Western population. Heterozygotes are prone to fas ting hypertriglyceridemia and low high density lipoprotein (HDL) cholestero l concentrations especially when secondary factors are superimposed on the genetic defect, We studied the LPL Asn291Ser gene variant as a modulator of postprandial lipemia in heterozygote carriers. Ten normolipidemic carriers were compared to ten control subjects, who were selected to have similar a ge, sex, BMI, and apolipoprotein (apo)E-phenotype. The subjects were given a lipid-rich mixed meal and their insulin sensitivity was determined by eug lycemic hyperinsulinemic clamp technique, The two groups had comparable fas ting triglycerides and glucose utilization rate during insulin infusion, bu t fasting HDL cholesterol tvas lo lower in carriers (1.25 +/- 0.05 mmol/L) than in the control subjects (1.53 +/- 0.06 mmol/L, P = 0.005), In the post prandial state the most pronounced differences were found in the very low d ensity lipoprotein 1 (VLDL1) fraction, where the carriers displayed higher responses of apoB-48 area under the curve (AUC), apoB-100 AUG, triglyceride AUG, and retinyl ester AUC than the control subjects, The most marked diff erences in apoB-48 and apoB-100 concentrations were observed late in the po stprandial period (9 and 12 h), demonstrating delayed clearance of triglyce ride-rich particles of both hepatic and intestinal origin, Postprandially, the carriers exhibited enrichment of triglycerides in HDL fraction. Thus, i n normolipidemic carriers the LPL Asn91Ser gene variant delays postprandial triglyceride, apoB-48, apoB-100, and retinyl ester metabolism iu VLDL1 fra ction and alters postprandial HDL composition compared to matched non-carri ers.