title: Effects of 34 risk loci for type 2 diabetes or hyperglycemia on lipoprotein subclasses and their composition in 6,580 nondiabetic Finnish men.
abstract: 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.
  
  
  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/m(2)). 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.
authors.affiliation: Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
authors.forename: Alena
authors.initials: A
authors.lastname: Stančáková
authors.forename: Jussi
authors.initials: J
authors.lastname: Paananen
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.forename: Lori L
authors.initials: LL
authors.lastname: Bonnycastle
authors.forename: Mario A
authors.initials: MA
authors.lastname: Morken
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
authors.forename: Anne U
authors.initials: AU
authors.lastname: Jackson
authors.forename: Michael L
authors.initials: ML
authors.lastname: Boehnke
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D015243:Cholesterol, VLDL / Q000097:blood; D000090943:Delta-5 Fatty Acid Desaturase; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics*; D044943:Fatty Acid Desaturases / Q000097:blood; D005838:Genotype; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood; D053419:Lipoproteins, IDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D051883:Receptor, Notch2 / Q000097:blood; D044465:White People
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015243:Cholesterol, VLDL; D000090943:Delta-5 Fatty Acid Desaturase; C485100:GCKR protein, human; D008075:Lipoproteins, HDL; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; C497764:NOTCH2 protein, human; D051883:Receptor, Notch2; D044943:Fatty Acid Desaturases; C000716847:FADS1 protein, human