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

Perez-Martinez, Pablo ; Corella, Dolores ; Shen, Jian ; Arnett, Donna K. ; Yiannakouris, Nikos ; Tai, E. Syong ; Orho-Melander, Marju LU ; Tucker, Katherine L. ; Tsai, Michael and Straka, Robert J. , et al. (2009) In American Journal of Clinical Nutrition 89(1). p.391-399
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... (More)
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. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Clinical Nutrition
volume
89
issue
1
pages
391 - 399
publisher
Elsevier
external identifiers
  • wos:000262262300049
  • scopus:58149389261
  • pmid:19056598
ISSN
1938-3207
DOI
10.3945/ajcn.2008.26363
language
English
LU publication?
yes
id
c27414e5-2db9-4dd8-9181-f0cf73ecf1c0 (old id 1313544)
date added to LUP
2016-04-01 13:28:06
date last changed
2025-01-03 10:33:55
@article{c27414e5-2db9-4dd8-9181-f0cf73ecf1c0,
  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 -&gt; T, APOA5 -1131T -&gt; C, and APOA5 56C -&gt; 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 &lt; 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.}},
  author       = {{Perez-Martinez, Pablo and Corella, Dolores and Shen, Jian and Arnett, Donna K. and Yiannakouris, Nikos and Tai, E. Syong and Orho-Melander, Marju and Tucker, Katherine L. and Tsai, Michael and Straka, Robert J. and Province, Michael and Kai, Chew Suok and Perez-Jimenez, Francisco and Lai, Chao-Qiang and Lopez-Miranda, Jose and Guillen, Marisa and Parnell, Laurence D. and Borecki, Ingrid and Kathiresan, Sekar and Ordovas, Jose M.}},
  issn         = {{1938-3207}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{391--399}},
  publisher    = {{Elsevier}},
  series       = {{American Journal of Clinical Nutrition}},
  title        = {{Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states}},
  url          = {{http://dx.doi.org/10.3945/ajcn.2008.26363}},
  doi          = {{10.3945/ajcn.2008.26363}},
  volume       = {{89}},
  year         = {{2009}},
}