THE ASSOCIATION BETWEEN FREE FATTY-ACID CONCENTRATIONS AND TRIGLYCERIDE-RICH LIPOPROTEINS IN THE POSTPRANDIAL STATE IS ALTERED BY A COMMON DELETION POLYMORPHISM OF THE APO-B SIGNAL PEPTIDE

To investigate whether there were associations between the free fatty acid (FFA) response during a fat tolerance test and changes in concent rations of triglyceride-rich lipoproteins 57 healthy Caucasian men bet ween 57 and 70 years of age underwent a fat tolerance test lasting 8 h . FFA concentrations initially decreased from 0.75 +/- 0.03 to 0.64 +/ - 0.03 mmol/l at 2 h and thereafter increased to 1.2 +/- 0.04 mmol/l a t 8 h. Maximum FFA concentration was the only significant determinant of 8 h triglyceride-rich lipoprotein (TGRLP) concentrations (pooled ch ylomicron and VLDL fractions d < 1.006) (TGRLP-TG r = 0.33, P = 0.012; TGRLP apo B r = 0.37, P = 0.004; TGRLP cholesterol r = 0.38, P = 0.00 4). The strength of the association between FFA and TGRLP was affected by the apo B signal peptide genotype. Only in individuals who were ho mozygous for the 27 amino acid (SP27 or I) allele of the apo B signal peptide were there significant associations between maximum FFA concen tration quartile and 8 h TGRLP concentration (P value for linear trend = 0.025). In this genotypic group there were lower HDL cholesterol co ncentrations (1.16 mmol/l compared to 1.38 mmol/ in subjects either he terozygous or homozygous for the SP24 [D] allele; P = 0.005) and there was a trend toward increased 8 h TGRLP concentrations. We propose tha t the association between post-prandial FFA. concentrations and post-p randial TGRLP concentrations in individuals who are homozygous for the SP27 allele may be linked to the increased prevalence of ischemic hea rt disease (IHD) in this genotypic group.