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Papers In Press, published online ahead of print January 1, 2010
J. Lipid Res., doi:10.1194/jlr.M800527-JLR200

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Journal of Lipid Research, Vol. 51, 63-73, January 2010
Copyright © 2010 by American Society for Biochemistry and Molecular Biology

Effects of variations in the APOA1/C3/A4/A5 gene cluster on different parameters of postprandial lipid metabolism in healthy young men^[S]

Javier Delgado-Lista^*, Francisco Perez-Jimenez^*, Juan Ruano^*, Pablo Perez-Martinez^*, Francisco Fuentes^*, Juan Criado-Garcia^*, Laurence D Parnell^**, Antonio Garcia-Rios^*, Jose M Ordovas^** and Jose Lopez-Miranda^1,*

^* Lipids and Atherosclerosis Research Unit, Reina Sofía University Hospital, Instituto Maimonides de Investigación Biomedica de Cordoba (IMIBIC), University of Cordoba, Ciber Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, CordobaSpain
^** Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA

¹ To whom correspondence should be addressed. e-mail: jlopezmir{at}uco.es

The APOA1/C3/A4/A5 gene cluster encodes important regulators of fasting lipids, but the majority of lipid metabolism takes place in the postprandial state and knowledge about gene regulation in this state is scarce. With the aim of characterizing possible regulators of lipid metabolism, we studied the effects of nine single nucleotide polymorphisms (SNPs) during postprandial lipid metabolism. Eighty-eight healthy young men were genotyped for APOA1 -2630 (rs613808), APOA1 -2803 (rs2727784), APOA1 -3012 (rs11216158), APOC3 -640 (rs2542052), APOC3 -2886 (rs2542051), APOC3 G34G (rs4520), APOA4 N147S (rs5104), APOA4 T29T (rs5092), and A4A5_inter (rs1263177) and were fed a saturated fatty acid-rich meal (1g fat/kg of weight with 60% fat, 15% protein and 25% carbohydrate). Serial blood samples were extracted for 11 h after the meal. Total cholesterol and fractions [HDL-cholesterol, LDL-cholesterol, trifacylglycerols (TGs) in plasma, TG-rich lipoproteins (TRLs) (large TRLs and small TRLs), apolipoprotein A-I and apolipoprotein B] were determined. APOA1 -2803 homozygotes for the minor allele and A4A5_inter carriers showed a limited degree of postprandial lipemia. Carriers of the rare alleles of APOA4 N147S and APOA4 T29T had lower APOA1 plasma concentration during this state. APOC3 -640 was associated with altered TG kinetics but not its magnitude. We have identified new associations between SNPs in the APOA1/C3/A4/A5 gene cluster and altered postprandial lipid metabolism.

Supplementary key words apolipoproteins • diet • gene-nutrient interaction • nutrigenomics • postprandial

Abbreviations: APOA1, apolipoprotein A1; APOC3, apolipoprotein C-III; APOA4, apolipoprotein A-IV; APOA5, apolipoprotein V; AUC, area under the curve; BMI, body mass index; CETP, cholesteryl ester transfer protein; CHOL, cholesterol; EBF1, early B-cell factor 1; HWE, Hardy-Weinberg equilibrium; LD, linkage disequilibrium; SNP, single nucleotide polymorphism; SRF, serum response factor; TG, triacylglycerol; TRL, TG-rich lipoprotein

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				J. Delgado-Lista, P. Perez-Martinez, F. Perez-Jimenez, A. Garcia-Rios, F. Fuentes, C. Marin, P. Gomez-Luna, A. Camargo, L. D. Parnell, J. M. Ordovas, et al. ABCA1 Gene Variants Regulate Postprandial Lipid Metabolism in Healthy Men Arterioscler Thromb Vasc Biol, May 1, 2010; 30(5): 1051 - 1057. [Abstract] [Full Text] [PDF]