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

Pablo Perez-Martinez, Dolores Corella, Jian Shen, Donna K. Arnett, Nikos Yiannakouris, E. Syong Tai, Marju Orho-Melander, Katherine L. Tucker, Michael Tsai, Robert J. Straka, Michael Province, Suok Kai Chew, Francisco Perez-Jimenez, Chao Qiang Lai, Jose Lopez-Miranda, Marisa Guillen, Laurence D. Parnell, Ingrid Borecki, Sekar Kathiresan, Jose M. Ordovas

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46 Scopus citations

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 rs780094C → T, APOA5 -1131T → C, and APOA5 56C → G 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.

Original languageEnglish (US)
Pages (from-to)391-399
Number of pages9
JournalAmerican Journal of Clinical Nutrition
Volume89
Issue number1
DOIs
StatePublished - Jan 1 2009

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