Effects of 34 Risk Loci for Type 2 Diabetes or Hyperglycemia on Lipoprotein Subclasses and Their Composition in 6,580 Nondiabetic Finnish Men
- Alena Stančáková1,
- Jussi Paananen1,
- Pasi Soininen2,3,
- Antti J. Kangas2,
- Lori L. Bonnycastle4,
- Mario A. Morken4,
- Francis S. Collins4,
- Anne U. Jackson5,
- Michael L. Boehnke5,
- Johanna Kuusisto1,
- Mika Ala-Korpela2,3,6 and
- Markku Laakso1⇓
- 1Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
- 2Computational Medicine Research Group, Institute of Clinical Medicine, University of Oulu and Biocenter Oulu, Oulu, Finland
- 3NMR Metabonomics Laboratory, Laboratory of Chemistry, Department of Biosciences, University of Eastern Finland, Kuopio, Finland
- 4National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
- 5Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan
- 6Department of Internal Medicine and Biocenter Oulu, Clinical Research Center, University of Oulu, Oulu, Finland
- Corresponding author: Markku Laakso, .
OBJECTIVE We investigated the effects of 34 genetic risk variants for hyperglycemia/type 2 diabetes on lipoprotein subclasses and particle composition in a large population-based cohort.
RESEARCH DESIGN AND METHODS The study included 6,580 nondiabetic Finnish men from the population-based Metabolic Syndrome in Men (METSIM) study (aged 57 ± 7 years; BMI 26.8 ± 3.7 kg/m2). Genotyping of 34 single nucleotide polymorphism (SNPs) for hyperglycemia/type 2 diabetes was performed. Proton nuclear magnetic resonance spectroscopy was used to measure particle concentrations of 14 lipoprotein subclasses and their composition in native serum samples.
RESULTS The glucose-increasing allele of rs780094 in GCKR was significantly associated with low concentrations of VLDL particles (independently of their size) and small LDL and was nominally associated with low concentrations of intermediate-density lipoprotein, all LDL subclasses, and high concentrations of very large and large HDL particles. The glucose-increasing allele of rs174550 in FADS1 was significantly associated with high concentrations of very large and large HDL particles and nominally associated with low concentrations of all VLDL particles. SNPs rs10923931 in NOTCH2 and rs757210 in HNF1B genes showed nominal or significant associations with several lipoprotein traits. The genetic risk score of 34 SNPs was not associated with any of the lipoprotein subclasses.
CONCLUSIONS Four of the 34 risk loci for type 2 diabetes or hyperglycemia (GCKR, FADS1, NOTCH2, and HNF1B) were significantly associated with lipoprotein traits. A GCKR variant predominantly affected the concentration of VLDL, and the FADS1 variant affected very large and large HDL particles. Only a limited number of risk loci for hyperglycemia/type 2 diabetes significantly affect lipoprotein metabolism.
- Received November 26, 2010.
- Accepted February 8, 2011.
- © 2011 by the American Diabetes Association.
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