Common variation in the gene for apolipoprotein B modulates postprandial lipoprotein metabolism: a hypothesis generating study.

We have carried out a pilot study to examine the influence on postprandial lipid and lipoprotein metabolism of common genetic variation in the gene coding for apolipoprotein (apo) B, in a previously described group of 30 individuals who had survived a myocardial infarction (MI) before the age of 45 (normo (NTG)- and hypertriglyceridaemic (HTG) patients) and 11 age-matched healthy individuals. Postprandial lipid or lipoprotein levels were examined by genotypes in the three groups separately and after adjustment for fasting triglycerides (TG) in the whole group combined. For the signal peptide polymorphism in the apo B gene, individuals with one or more SP-24 alleles had a 38% smaller mean area under curve (AUC) (P = 0.06) for postprandial large chylomicron remnants and a 29% smaller mean AUC (P = 0.01) for large very low density lipoproteins (VLDLs) compared to individuals homozygous for the wild type SP-27 allele. Previously in this patient group, small chylomicron remnants (apo B-48 levels in the Sf 20-60 range) were found to relate significantly and positively to progression of coronary atherosclerosis suggesting that these lipoproteins are implicated in progression of atherosclerosis. For the apo B Val591-Ala polymorphism (Ag a1/d), individuals homozygous for the V591 allele had a 33% greater AUC for Sf 20-60 postprandial triglycerides (P = 0.006), with higher postprandial levels of both apo B-48- and apo B-100-containing lipoproteins in this fraction. This pilot study gives insight into the mechanisms of the previously reported associations between polymorphisms in the apo B gene and fasting plasma lipids and lipoproteins.