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


METHODS
We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7,730 men and women) and 2 intervention studies in US whites (n = 1,061) 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.
Perez-Martinez
Pablo
P
Nutrition and Genomics Laboratory, Jean Mayer-US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA. pablopermar@yahoo.es
Corella
Dolores
D
Shen
Jian
J
Arnett
Donna K
DK
Yiannakouris
Nikos
N
Tai
E Syong
ES
Orho-Melander
Marju
M
Tucker
Katherine L
KL
Tsai
Michael
M
Straka
Robert J
RJ
Province
Michael
M
Kai
Chew Suok
CS
Perez-Jimenez
Francisco
F
Lai
Chao-Qiang
CQ
Lopez-Miranda
Jose
J
Guillen
Marisa
M
Parnell
Laurence D
LD
Borecki
Ingrid
I
Kathiresan
Sekar
S
Ordovas
Jose M
JM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D003430:Cross-Sectional Studies; D004041:Dietary Fats / Q000008:administration & dosage / Q000378:metabolism; D005215:Fasting / Q000097:blood; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019518:Postprandial Period; D012307:Risk Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood* / Q000235:genetics; D055815:Young Adult
C437704:APOA5 protein, human; D048868:Adaptor Proteins, Signal Transducing; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D004041:Dietary Fats; C485100:GCKR protein, human; D000960:Hypolipidemic Agents; D014280:Triglycerides; D011345:Fenofibrate