title: Glucokinase regulatory protein gene polymorphism affects postprandial lipemic response in a dietary intervention study.
abstract: Postprandial triglyceridemia is an emerging risk factor for cardiovascular disease. However, most of the genes that influence postprandial triglyceridemia are not known. We evaluated whether a common nonsynonymous SNP rs1260326/P446L in the glucokinase regulatory protein (GCKR) gene influenced variation in the postprandial lipid response after a high-fat challenge in seven hundred and seventy participants in the Amish HAPI Heart Study who underwent an oral high-fat challenge and had blood samples taken in the fasting state and during the postprandial phase at 1, 2, 3, 4, and 6 h. We found that the minor T allele at rs1260326 was associated with significantly higher fasting TG levels after adjusting for age, sex, and family structure (P (a) = 0.06 for additive model, and P (r) = 0.0003 for recessive model). During the fat challenge, the T allele was associated with significantly higher maximum TG level (P (a) = 0.006), incremental maximum TG level (P (a) = 0.006), TG area under the curve (P (a) = 0.02) and incremental TG area under the curve (P (a) = 0.03). Our data indicate that the rs1260326 T allele of GCKR is associated with both higher fasting levels of TG as well as the postprandial TG response, which may result in higher atherogenic risk.
authors.affiliation: Division of Endocrinology, Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, 660 West Redwood Street, Rm. 494, Baltimore, MD 21201, USA. hshen@medicine.umaryland.edu
authors.forename: Haiqing
authors.initials: H
authors.lastname: Shen
authors.forename: Toni I
authors.initials: TI
authors.lastname: Pollin
authors.forename: Coleen M
authors.initials: CM
authors.lastname: Damcott
authors.forename: John C
authors.initials: JC
authors.lastname: McLenithan
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D004041:Dietary Fats / Q000008:administration & dosage*; D005215:Fasting; D005260:Female; D005838:Genotype; D005941:Glucokinase / Q000235:genetics*; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D019518:Postprandial Period / Q000235:genetics*; D012307:Risk Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004041:Dietary Fats; C485100:GCKR protein, human; D008055:Lipids; D014280:Triglycerides; D005941:Glucokinase