Advanced

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)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
American Journal of Clinical Nutrition
volume
89
issue
1
pages
391 - 399
publisher
American Society for Clinical Nutrition
external identifiers
  • wos:000262262300049
  • scopus:58149389261
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
2009-03-10 08:37:34
date last changed
2017-07-30 04:03:07
@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    = {American Society for Clinical Nutrition},
  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},
  volume       = {89},
  year         = {2009},
}