Glucokinase regulatory protein gene polymorphism affects postprandial lipemic response in a dietary intervention study

Hum Genet. 2009 Oct;126(4):567-74. doi: 10.1007/s00439-009-0700-3. Epub 2009 Jun 13.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adult
  • Dietary Fats / administration & dosage*
  • Fasting
  • Female
  • Genotype
  • Glucokinase / genetics*
  • Humans
  • Lipids / analysis*
  • Male
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*
  • Postprandial Period / genetics*
  • Risk Factors
  • Triglycerides / metabolism


  • Adaptor Proteins, Signal Transducing
  • Dietary Fats
  • GCKR protein, human
  • Lipids
  • Triglycerides
  • Glucokinase