Abstract
Apolipoprotein (apoB) plays a fundamental role in the transport and metabolism of plasma triacylglycerols (TAGs) and cholesterol. Several apoB polymorphic sites have been studied for their potential use as markers for coronary heart disease in the population. In view of the importance of apoB in postprandial metabolism, our objective was to determine whether the presence of the -516C/T polymorphism in the APOB gene promoter could influence postprandial lipoprotein metabolism in healthy subjects. Forty-seven volunteers who were homozygous for the E3 allele at the APOE gene were selected (30 homozygous for the common genotype (C/C) and 17 heterozygotes for the -516T allele (C/T). They were given a fat-rich meal containing 1 g fat and 7 mg cholesterol per kg body weight and vitamin A 60,000 IU/m2 body surface. Fat accounted for 60% of calories, and protein and carbohydrates for 15 and 25% of energy, respectively. Blood samples were taken at time 0, every 1 h until 6 h, and every 2.5 h until 11 h. Total cholesterol and TAGs in plasma, and cholesterol, TAGs and retinyl palmitate in triacylglycerol-rich lipoproteins (large and small triacylglycerol-rich lipoproteins) were determined by ultracentrifugation. Individuals carrying the C/T genotype presented greater postprandial concentrations of TAGs in small triacylglycerol-rich lipoproteins than did carriers of the C/C genotype (P = 0.022). Moreover, C/T individuals presented higher concentrations of plasma TAGs during the postprandial period than did C/C subjects (P = 0.039). No other statistically significant genotype-related differences for other parameters were observed. These results suggest that the presence of the genotype C/T is associated with a higher postprandial response. Thus, the allele variability in the -516C/T polymorphism in the APOB gene promoter may partly explain the interindividual differences in postprandial lipemic response in healthy subjects.
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Abbreviations
- apoB:
-
Apolipoprotein B
- BMI:
-
Body mass index
- CHO:
-
Carbohydrate
- CHD:
-
Coronary heart disease
- LDL:
-
Low-density lipoprotein
- MUFA:
-
Monounsaturated fatty acid
- SFA:
-
Saturated fatty acid
- TAGs:
-
Triacylglycerol
- TRL:
-
Triacylglycerol-rich lipoproteins
References
Kugiyama K, Doi H, Takazoe K, Kawano H, Soejima H, Mizuno Y, Tsunoda R, Sakamoto T, Nakano T, Nakajima K, Ogawa H, Sugiyama S, Yoshimura M, Yasue H (1999) Remnant lipoprotein levels in fasting serum predict coronary events in patients with coronary artery disease. Circulation 8:2858–2860
Ooi TC, Cousins M, Ooi DS, Steiner G, Uffelman KD, Nakajima K, Simo IE (2001) Postprandial remnant-like lipoproteins in hypertriglyceridemia. J Clin Endocrinol Metab 86:3134–3142
Boquist S, Ruotolo G, Tang R, Bjorkegren J, Bond MG, de Faire U, Karpe F, Hamsten A (1999) Alimentary lipemia, postprandial triglyceride-rich lipoproteins, and common carotid intima-media thickness in healthy, middle-aged men. Circulation 100:723–728
Karpe F, Hellenius ML, Hamsten A (1999) Differences in postprandial concentrations of very-low-density lipoprotein and chylomicron remnants between normotriglyceridemic and hypertriglyceridemic men with and without coronary heart disease. Metabolism 48:301–307
Fukushima H, Sugiyama S, Honda O, Koide S, Nakamura S, Sakamoto T, Yoshimura M, Ogawa H, Fujioka D, Kugiyama K (2004) Prognostic value of remnant-like lipoprotein particle levels in patients with coronary artery disease and type II diabetes mellitus. J Am Coll Cardiol 43:2219–2224
Kolovou GD, Anagnostopoulou KK, Pavlidis AN, Salpea KD, Iraklianou SA, Tsarpalis K, Damaskos DS, Manolis A, Cokkinos DV (2005) Postprandial lipemia in men with metabolic syndrome, hypertensives and healthy subjects. Lipids Health Dis 4:21
Hamsten A, Silveira A, Boquist S, Tang R, Bond MG, de Faire U, Bjorkegren J (2005) The apolipoprotein CI content of triglyceride-rich lipoproteins independently predicts early atherosclerosis in healthy middle-aged men. J Am Coll Cardiol 45:1013–1017
Ordovas JM (2001) Genetics, postprandial lipemia and obesity. Nutr Metab Cardiovasc Dis 11:118–133
Lopez-Miranda J, Perez-Martinez P, Marin C, Moreno JA, Gomez P, Perez-Jimenez F (2006) Postprandial lipoprotein metabolism, genes and risk of CVD. Curr Opin Lipidol 17:132–138
Genest JJ Jr, Ordovas JM, McNamara JR, Robbins AM, Meade T, Cohn SD, Salem DN, Wilson PW, Masharani U, Frossard PM (1990) DNA polymorphisms of the apolipoprotein B gene in patients with premature coronary artery disease. Atherosclerosis 82:7–17
Lopez-Miranda J, Ordovas JM, Ostos MA, Marin C, Jansen S, Salas J, Blanco-Molina A, Jimenez-Pereperez JA, Lopez-Segura F, Perez-Jimenez F (1997) Dietary fat clearance in normal subjects is modulated by genetic variation at the apolipoprotein B gene locus. Arterioscler Thromb Vasc Biol 17:1765–1773
Boerwinkle E, Chan L (1989) A three codon insertion/deletion polymorphism in the signal peptide region of the human apolipoprotein B (APOB) gene directly typed by the polymerase chain reaction. Nucleic Acids Res 25:4003
Regis-Bailly A, Fournier B, Steinmetz J, Gueguen R, Siest G, Visvikis S (1995) Apo B signal peptide insertion/deletion polymorphism is involved in postprandial lipoparticles’ responses. Atherosclerosis 118:23–34
Van ‘t Hooft FM, Jormsjo S, Lundahl B, Tornvall P, Eriksson P, Hamsten A (1999) A functional polymorphism in the apolipoprotein B promoter that influences the level of plasma low density lipoprotein. J Lipid Res 40:1686–1694
Olofsson SO, Boren J (2005) Apolipoprotein B: a clinically important apolipoprotein which assembles atherogenic lipoproteins and promotes the development of atherosclerosis. J Intern Med 258:395–410
Perez-Martinez P, Perez-Jimenez F, Ordovas JM, Moreno JA, Moreno R, Fuentes F, Ruano J, Gomez P, Marin C, Lopez-Miranda J (2007) The APOB -516C/T polymorphism is associated with differences in insulin sensitivity in healthy males, during the consumption of diets with different fat contents. Br J Nutr (in press)
Boerwinkle E, Brown S, Sharrett AR, Heiss G, Patsch W (1994) Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations. Am J Hum Genet 54:341–360
Bucolo G, David H (1973) Quantitative determination of serum triglycerides by use of enzymes. Clin Chem 19:476–482
Allain CC, Poon LS, Chang CSG, Richmond W, Fu PC (1974) Enzymatic determination of total serum cholesterol. Clin Chem 20:470–475
Riepponen P, Marniemi J, Rautaoja T (1987) Immunoturbidimetric determination of apolipoproteins A-1 and B in serum. Scand J Clin Lab Invest 47:739–744
Warnick R, Benderson J, Albers JJ (1982) Dextran Sulfate-Mg precipitation procedure for quantitation of high density lipoprotein cholesterol. Clin Chem 28:1379–1388
Ruotolo G, Zhang H, Bentsianov V, Le NA (1992) Protocol for the study of the metabolism of retinyl esters in plasma lipoproteins during postprandial lipemia. J Lipid Res 33:1541-1549
De Ruyter MGM, De Leeheer AP (1978) Simultaneous determination of retinol and retinyl esters in serum or plasma by reversed-phase high performance liquid chromatography. Clin Chem 24:1920–1923
Karpe F, Hamsten A (1994) Determination of apolipoproteins B-48 and B-100 in triglyceride-rich lipoproteins by analytical SDS-PAGE. J Lipid Res 35:1311–1317
Patsch JR, Miesenbock G, Hopferwieser T, Muhlberger V, Knapp E, Dunn JK, Gotto AM Jr, Patsch W (1992) Relation of triglyceride metabolism and coronary artery disease: studies in the postprandial state. Arterioscler Thromb 12:1336–1345
Phillips NR, Waters D, Havel RJ (1993) Plasma lipoproteins and progression of coronary artery disease evaluated by angiography and clinical events. Circulation 88:2762–2770
Perez-Martinez P, Perez-Jimenez F, Ordovas JM, Bellido C, Moreno JA, Gomez P, Marin C, Fernandez de la Puebla RA, Paniagua JA, and Lopez-Miranda J (2007) The APOB -516C/T polymorphism has no effect on lipid and apolipoprotein response following changes in dietary fat intake in a healthy population. Nutr Metab Cardiovasc Dis (in press)
Pimstone SN, Clee SM, Gagné E., Miao L, Zhang H, Stein EA, Hayden MR (1996) A frequently occurring mutation in the lipoprotein lipase gene (Asn291Ser) results in altered postprandial chylomicron triglyceride and retinyl palmitate response in normolipidemic carriers. J Lipid Res 37:1675–1684
Ostos MA, Lopez-Miranda J, Ordovas JM, Marin C, Blanco A, Castro P, Lopez-Segura F, Jimenez-Pereperez J, Perez-Jimenez F (1998) Dietary fat clearance is modulated by genetic variation in apolipoprotein A-IV gene locus. J Lipid Res 39:2493–2500
Boerwinkle E, Brown S, Sharrett AR, Heiss G, Patsch W (1994) Apolipoprotein E polymorphism influences postprandial retinyl palmitate but not triglyceride concentrations. Am J Hum Genet 54:341–360
Abbasi F, McLaughlin T, Lamendola C, Yeni-Komshian H, Tanaka A, Wang T, Nakajima K, Reaven GM (1999) Fasting remnant lipoprotein cholesterol and triglyceride concentrations are elevated in nondiabetic, insulin-resistant, female volunteers. J Clin Endocrinol Metab 84:3903–3906
Ai M, Tanaka A, Ogita K, Sekine M, Numano F, Numano F, Reaven GM (2001) Relationship between insulin concentration and plasma remnant lipoprotein response to an oral fat load in patients with type 2 diabetes. J Am Coll Cardiol 38:1628–1632
Harbis A, Perdreau S, Vincent-Baudry S, Charbonnier M, Bernard MC, Raccah D, Senft M, Lorec AM, Defoort C, Portugal H, Vinoy S, Lang V, Lairon D (2004) Glycemic and insulinemic meal responses modulate postprandial hepatic and intestinal lipoprotein accumulation in obese, insulin-resistant subjects. Am J Clin Nutr 80:896–902
Tanaka A (2004) Postprandial hyperlipidemia and atherosclerosis. J Atheroscler Thromb 11:322–329
Wilson DE, Chan IF, Buchi KN, Horton SC (1985) Postchallenge plasma lipoprotein retinoids: chylomicron remnants in endogenous hypertriglyceridemia. Metabolism 34:551–558
Sposito AC, Gonbert S, Turpin G, Chapman MJ, Thillet J (2004) Common promoter C516T polymorphism in the ApoB gene is an independent predictor of carotid atherosclerotic disease in subjects presenting a broad range of plasma cholesterol levels. Arterioscler Thromb Vasc Biol 24:2192–2195
Vohl MC, Lamarche B, Moorjani S, Prud‘homme D, Nadeau A, Bouchard C, Lupien PJ, Despres JP (1995) The lipoprotein lipase HindIII polymorphism modulates plasma triglyceride levels in visceral obesity. Arterioscler Thromb Vasc Biol 15:714–720
Acknowledgment
This work was supported by research grants from the CIBER CBO/6/03, Instituto de Salud Carlos III; Plan Nacional de Investigación (Ministerio de Educación y Ciencia) (SAF 01/2466-C05 04 to F P-J, SAF 01/0366 to J L-M); the Spanish Ministry of Health (FIS 01/0449); Consejería de Salud, Servicio Andaluz de Salud (00/212, 00/39, 01/239, 01/243, 02/64, 02/65, 02/78), Consejería de Educación, Plan Andaluz de Investigación, Universidad de Córdoba and by NIH/NHLBI grant no. HL54776 and contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research Service.
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Pérez-Martínez, P., Pérez-Jiménez, F., Ordovás, J.M. et al. Postprandial Lipemia is Modified by the Presence of the APOB-516C/T Polymorphism in a Healthy Caucasian Population. Lipids 42, 143–150 (2007). https://doi.org/10.1007/s11745-007-3027-7
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DOI: https://doi.org/10.1007/s11745-007-3027-7