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Photo: KG Pressfoto

Marju Orho-Melander

Professor

Photo: KG Pressfoto

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

Author

  • 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
  • Chew Suok Kai
  • Francisco Perez-Jimenez
  • Chao-Qiang Lai
  • Jose Lopez-Miranda
  • Marisa Guillen
  • Laurence D. Parnell
  • Ingrid Borecki
  • Sekar Kathiresan
  • Jose M. Ordovas

Summary, in English

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. Am J Clin Nutr 2009;89:391-9. Clin Nutr 2009; 89: 391-9.

Department/s

  • Genomics, Diabetes and Endocrinology

Publishing year

2009

Language

English

Pages

391-399

Publication/Series

American Journal of Clinical Nutrition

Volume

89

Issue

1

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Nutrition and Dietetics

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1938-3207