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

2009; Springer Science+Business Media; Volume: 126; Issue: 4 Linguagem: Inglês

10.1007/s00439-009-0700-3

1432-1203

Haiqing Shen, Toni I. Pollin, Coleen Damcott, John C. McLenithan, Braxton D. Mitchell, Alan R. Shuldiner,

Genetic Associations and Epidemiology

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.