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This Article Full Text (Publish Ahead of Print[PDF]) All Versions of this Article: 89/1/391    most recent ajcn.2008.26363v1 Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Perez-Martinez, P. Articles by Ordovas, J. M Search for Related Content PubMed PubMed Citation Articles by Perez-Martinez, P. Articles by Ordovas, J. M Agricola Articles by Perez-Martinez, P. Articles by Ordovas, J. M

Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states^1,2,3

¹ From the Nutrition and Genomics Laboratory (PP-M, DC, JS, C-QL, LDP, and JMO) and the Dietary Assessment and Epidemiology Research Program (KLT), Jean Mayer–US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA; the Reina Sofia University Hospital, Lipids and Atherosclerosis Research Unit and CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), University of Cordoba, Cordoba, Spain (PP-M, FP-J, and JL-M); the Genetic and Molecular Epidemiology Unit and CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), School of Medicine, University of Valencia, Valencia, Spain (DC and MG); the Department of Epidemiology, University of Alabama, Birmingham, AL (DKA); the Harokopio University of Athens, Athens, Greece (NY); the Department of Endocrinology, Singapore General Hospital, Singapore (EST); the Department of Clinical Sciences, University Hospital Malmö, Clinical Research Center, Lund University, Malmö, Sweden (MO-M); the Departments of Laboratory Medicine and Pathology (MT) and Experimental and Clinical Pharmacology (RJS), University of Minnesota, Minneapolis, MN; the Division of Biostatistics, Washington University School of Medicine, St Louis, MO (MP and IB); the Epidemiology and Disease Control Division, Ministry of Health, Singapore (CSK); and the Cardiovascular Disease Prevention Center, Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA (SK).

² Supported by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Agricultural Research Service; NIH Heart, Lung, and Blood Institute grant U 01 HL72524, Genetic and Environmental Determinants of Triglycerides; NIH, National Institute on Aging, grant 5P01AG023394-02; RD07/0067/0006 (ISCIII) and PR2008-0268 (MICIN); and CIBEROBN03/06 and PI070954 from the Instituto de Salud Carlos III, Spain.

³ Reprints not avalible. Address correspondence to P Perez-Martinez, Reina Sofia University Hospital, Lipids and Atherosclerosis Research Unit, Avda Menéndez Pidal, s/n 14004 Córdoba, Spain. E-mail: pablopermar{at}yahoo.es.

ABSTRACT

Background: Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma triacylglycerol.

Objective: We investigated the combined effects of the GCKR rs780094CT, APOA5 –1131TC, and APOA5 56CG single nucleotide polymorphisms (SNPs) on fasting triacylglycerol in several independent populations and the response to a high-fat meal and fenofibrate interventions.

Design: We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7730 men and women) and 2 intervention studies in US whites (n = 1061) to examine postprandial triacylglycerol after a high-fat meal and the response to fenofibrate. We defined 3 combined genotype groups: 1) protective (homozygous for the wild-type allele for all 3 SNPs); 2) intermediate (any mixed genotype not included in groups 1 and 3); and 3) risk (carriers of the variant alleles at both genes).

Results: Subjects within the risk group had significantly higher fasting triacylglycerol and a higher prevalence of hypertriglyceridemia than did subjects in the protective group across all populations. Moreover, subjects in the risk group had a greater postprandial triacylglycerol response to a high-fat meal and greater fenofibrate-induced reduction of fasting triacylglycerol than did the other groups, especially among persons with hypertriglyceridemia. Subjects with the intermediate genotype had intermediate values (P for trend <0.001).

Conclusions: SNPs in GCKR and APOA5 have an additive effect on both fasting and postprandial triacylglycerol and contribute to the interindividual variability in response to fenofibrate treatment.

Received for publication May 3, 2008. Accepted for publication September 19, 2008.