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

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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.

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Acknowledgments

This work supported by NIH research grants U01 HL72515, the University of Maryland General Clinical Research Center, grant M01 RR 16500, the Clinical Nutrition Research Unit of Maryland (P30 DK072488), the Baltimore Diabetes Research and Training Center grant (P60 DK079637), and the Baltimore Veterans Administration Medical Center Geriatrics Research and Education Clinical Center. We thank our Amish research volunteers for their long-standing partnership in research, and the research staff at the Amish Research Clinic for their hard work and dedication.

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  1. 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

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

  2. Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD, USA

    Alan R. Shuldiner

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  1. Haiqing Shen
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  2. Toni I. Pollin
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Correspondence to Alan R. Shuldiner.

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Shen, H., Pollin, T.I., Damcott, C.M. et al. Glucokinase regulatory protein gene polymorphism affects postprandial lipemic response in a dietary intervention study. Hum Genet 126, 567–574 (2009). https://doi.org/10.1007/s00439-009-0700-3

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