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RESEARCH PRODUCT
Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states.
Jose Lopez-mirandaJose M. OrdovasChew Suok KaiMarisa GuillénRobert J. StrakaIngrid B. BoreckiDonna K. ArnettKatherine L. TuckerSekar KathiresanMichael Y. TsaiDolores CorellaMarju Orho-melanderChao-qiang LaiMichael A. ProvinceFrancisco Pérez-jiménezPablo Perez-martinezLaurence D. ParnellE Syong TaiJian ShenNikos Yiannakourissubject
AdultMalemedicine.medical_specialtyGenotypeGene-Nutrient InteractionsMedicine (miscellaneous)Blood lipidsSingle-nucleotide polymorphismPolymorphism Single NucleotideYoung AdultFenofibrateGene FrequencyRisk FactorsInternal medicineHyperlipidemiamedicineHumansGenetic Predisposition to DiseaseApolipoproteins ATriglyceridesAdaptor Proteins Signal TransducingAgedHypolipidemic AgentsHypertriglyceridemiaNutrition and DieteticsFenofibrateGlucokinase regulatory proteinbiologyGlucokinaseHypertriglyceridemianutritional and metabolic diseasesGenetic VariationFastingMiddle Agedmedicine.diseasePostprandial PeriodDietary FatsPostprandialEndocrinologyCross-Sectional StudiesTreatment OutcomeApolipoprotein A-Vbiology.proteinlipids (amino acids peptides and proteins)Femalemedicine.drugdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2008-12-06 | The American journal of clinical nutrition |