title: The association between free fatty acid concentrations and triglyceride-rich lipoproteins in the post-prandial state is altered by a common deletion polymorphism of the apo B signal peptide.
abstract: To investigate whether there were associations between the free fatty acid (FFA) response during a fat tolerance test and changes in concentrations of triglyceride-rich lipoproteins 57 healthy Caucasian men between 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 at 8 h. Maximum FFA concentration was the only significant determinant of 8 h triglyceride-rich lipoprotein (TGRLP) concentrations (pooled chylomicron 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 = 0.004). The strength of the association between FFA and TGRLP was affected by the apo B signal peptide genotype. Only in individuals who were homozygous for the 27 amino acid (SP27 or I) allele of the apo B signal peptide were there significant associations between maximum FFA concentration quartile and 8 h TGRLP concentration (P value for linear trend = 0.025). In this genotype group there were lower HDL cholesterol concentrations (1.16 mmol/l compared to 1.38 mmol/l in subjects either heterozygous or homozygous for the SP24 [D] allele; P = 0.005) and there was a trend toward increased 8 h TGRLP concentrations. We propose that the association between post-prandial FFA concentrations and post-prandial TGRLP concentrations in individuals who are homozygous for the SP27 allele may be linked to the increased prevalence of ischemic heart disease (IHD) in this genotypic group.
authors.affiliation: University Department of Clinical Biochemistry, Addenbrookes Hospital, Cambridge, UK. cdtb@mole.bio.cam.ac.uk
authors.forename: C D
authors.initials: CD
authors.lastname: Byrne
authors.forename: N J
authors.initials: NJ
authors.lastname: Wareham
authors.forename: P K
authors.initials: PK
authors.lastname: Mistry
authors.forename: D I
authors.initials: DI
authors.lastname: Phillips
authors.forename: N D
authors.initials: ND
authors.lastname: Martensz
authors.forename: D
authors.initials: D
authors.lastname: Halsall
authors.forename: P J
authors.initials: PJ
authors.lastname: Talmud
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
authors.forename: C N
authors.initials: CN
authors.lastname: Hales
mesh_terms: D000368:Aged; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics*; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D002914:Chylomicrons / Q000097:blood / Q000235:genetics; D004247:DNA / Q000032:analysis; D005230:Fatty Acids, Nonesterified / Q000097:blood* / Q000235:genetics; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D015592:Immunoradiometric Assay; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019518:Postprandial Period; D015995:Prevalence; D021382:Protein Sorting Signals / Q000097:blood / Q000235:genetics*; D012016:Reference Values; D014280:Triglycerides / Q000097:blood* / Q000235:genetics; D014461:Ultracentrifugation
chemical_list: D001055:Apolipoproteins B; D002914:Chylomicrons; D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL; D021382:Protein Sorting Signals; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D004247:DNA