This Article Full Text Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jansen, S. Articles by Perez-Jimenez, F. Search for Related Content PubMed PubMed Citation Articles by Jansen, S. Articles by Perez-Jimenez, F.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1532-1538.)
© 1997 American Heart Association, Inc.

Articles

Effect of 347-Serine Mutation in Apoprotein A-IV on Plasma LDL Cholesterol Response to Dietary Fat

Sergio Jansen; Jose Lopez-Miranda; Joaquin Salas; Jose M. Ordovas; Pedro Castro; Carmen Marin; Maria A. Ostos; Fernando Lopez-Segura; Jose A. Jimenez-Pereperez; Angeles Blanco; ; Francisco Perez-Jimenez

From the Lipid Research Unit, University Hospital "Reina Sofía," University of Córdoba Medical School, Córdoba, Spain, and The Lipid Metabolism Laboratory, US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Mass (J.M.O.).

Correspondence to Dr Francisco Perez-Jimenez, Departamento de Patologia Médica, Facultad de Medicina de Córdoba, Avenida Menéndez Pidal s/n, Córdoba 14004, Spain.

Abstract Lipid response to dietary fat and cholesterol is, to a large extent, genetically controlled. Apoprotein (apo) A-IV has been related to fat absorption and to the activation of some of the enzymes involved in lipid metabolism. One mutation has been described in the apo A-IV gene that causes substitution of Ser for Thr at position 347. To study the influence of this mutation on the plasma LDL cholesterol (LDL-C) response in diets of various fat content and fatty acid saturation, 41 healthy male subjects were studied, 25 of whom were homozygous for the Thr allele (347Thr) and the rest who were either homozygous (n=2) or heterozygous carriers of the Ser allele (347Ser). They consumed three consecutive diets, each of 4 weeks' duration: one rich in saturated fat (SFA diet: 38% fat, 20% saturated), a National Cholesterol Education Program (NCEP) type 1 diet (28% fat, 10% saturated), and a third rich in monounsaturated fat (MUFA diet; 38% fat, 22% monounsaturated). Carriers of the 347Ser allele presented a greater decrease in total cholesterol (-0.7 vs -0.44 mmol/L, P<.034), LDL-C (-0.62 vs -0.31 mmol/L, P<.012), and apo B (-14 vs -8 mg/dL, P<.01) levels when they were switched from the SFA to the NCEP type 1 diet than homozygous carriers of the 347Thr allele. The change from the NCEP type 1 to the MUFA diet resulted in a greater increase in total cholesterol (0.18 vs -0.05 mmol/L, P<.028) and apo B (5 vs -1 mg/dL, P<.006) levels in the 347Ser than in the 347Thr individuals. In a previous study, we demonstrated that the GA polymorphism at position -76 of the gene promoter of apo A-I affects the LDL-C response to dietary fat. We therefore decided to study the effect of the interaction between these mutations on this response. We found that both mutations have an additive effect on total cholesterol, LDL-C, and apo B dietary-induced changes. Our results suggest that total cholesterol and LDL-C response to dietary fat is influenced by the 347Ser mutation of apo A-IV.

Key Words: apolipoprotein A-IV • diet • genetic polymorphism • cholesterol

This article has been cited by other articles:

				J. Lopez-Miranda, G. Cruz, P. Gomez, C. MarIn, E. Paz, P. Perez-MartInez, F. J. Fuentes, J. M. Ordovas, and F. Perez-Jimenez The Influence of Lipoprotein Lipase Gene Variation on Postprandial Lipoprotein Metabolism J. Clin. Endocrinol. Metab., September 1, 2004; 89(9): 4721 - 4728. [Abstract] [Full Text] [PDF]

				L. F Masson, G. McNeill, and A. Avenell Genetic variation and the lipid response to dietary intervention: a systematic review Am. J. Clinical Nutrition, May 1, 2003; 77(5): 1098 - 1111. [Abstract] [Full Text] [PDF]

				K. J. Hockey, R. A. Anderson, V. R. Cook, R. R. Hantgan, and R. B. Weinberg Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance J. Lipid Res., February 1, 2001; 42(2): 211 - 217. [Abstract] [Full Text]

				R. B. Weinberg, B. W. Geissinger, K. Kasala, K. J. Hockey, J. G. Terry, L. Easter, and J. R. Crouse Effect of apolipoprotein A-IV genotype and dietary fat on cholesterol absorption in humans J. Lipid Res., December 1, 2000; 41(12): 2035 - 2041. [Abstract] [Full Text]

				R. M. Weggemans, P. L. Zock, S. Meyboom, H. Funke, and M. B. Katan Apolipoprotein A4-1/2 polymorphism and response of serum lipids to dietary cholesterol in humans J. Lipid Res., October 1, 2000; 41(10): 1623 - 1628. [Abstract] [Full Text]

				R. M. Fisher, H. Burke, V. Nicaud, C. Ehnholm, and S. E. Humphries Effect of variation in the apo A-IV gene on body mass index and fasting and postprandial lipids in the European Atherosclerosis Research Study II J. Lipid Res., February 1, 1999; 40(2): 287 - 294. [Abstract] [Full Text]

				M. A. Ostos, J. Lopez-Miranda, J. M. Ordovas, C. Marin, A. Blanco, P. Castro, F. Lopez-Segura, J. Jimenez-Pereperez, and F. Perez-Jimenez Dietary fat clearance is modulated by genetic variation in apolipoprotein A-IV gene locus J. Lipid Res., December 1, 1998; 39(12): 2493 - 2500. [Abstract] [Full Text]

				R. Carmena-Ramon, J. F. Ascaso, J. T. Real, J. M. Ordovas, and R. Carmena Genetic Variation at the ApoA-IV Gene Locus and Response to Diet in Familial Hypercholesterolemia Arterioscler. Thromb. Vasc. Biol., August 1, 1998; 18(8): 1266 - 1274. [Abstract] [Full Text] [PDF]

				S. Jansen, J. Lopez-Miranda, J. Salas, P. Castro, J. A. Paniagua, F. Lopez-Segura, J. M. Ordovas, J. A. Jimenez-Pereperez, A. Blanco, and F. Perez-Jimenez Plasma Lipid Response to Hypolipidemic Diets in Young Healthy Non-Obese Men Varies with Body Mass Index J. Nutr., July 1, 1998; 128(7): 1144 - 1149. [Abstract] [Full Text] [PDF]