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

Research output: Contribution to journalArticlepeer-review

50 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
Pages (from-to)391-399
Number of pages9
JournalAmerican Journal of Clinical Nutrition
Volume89
Issue number1
DOIs
StatePublished - Jan 1 2009

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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