title: Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population: Mendelian randomization study.
abstract: BACKGROUND
  Low plasma 25-hydroxyvitamin D [25(OH)D] levels are associated with high cardiovascular risk. This may be because that low 25(OH)D levels are associated with high levels of atherogenic lipoproteins, but whether these 2 risk factors are genetically associated is unknown. We tested this hypothesis.
  
  
  RESULTS
  Using a Mendelian randomization approach, potential genetic associations between plasma levels of atherogenic lipoproteins and 25(OH)D were examined in ≤85,868 white, Danish individuals in whom we genotyped for variants affecting plasma levels of 25(OH)D, nonfasting remnant cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Lipoprotein levels were measured in all and 25(OH)D levels in 31,435. A doubling in nonfasting remnant cholesterol levels was observationally and genetically associated with -6.0%(95% confidence interval [CI], -6.5% to -5.5%) and -8.9% (95% CI, -15% to -2.3%) lower plasma 25(OH)D levels. For low-density lipoprotein-cholesterol levels, corresponding values were -4.6% (95% CI, -5.4% to -3.7%) observationally and -11% (95% CI, -29% to +6.9%) genetically. In contrast, a halving in high-density lipoprotein-cholesterol levels was observationally associated with -1.5% (95% CI, -2.2% to -0.7%) lower but genetically associated with +20% (95% CI, +7.4% to +34%) higher plasma 25(OH)D levels. Plasma levels of lipoprotein(a) and 25(OH)D did not associate. Finally, low 25(OH)D levels did not associate genetically with levels of remnant and low-density lipoprotein-cholesterol.
  
  
  CONCLUSIONS
  Genetically elevated nonfasting remnant cholesterol is associated with low 25(OH)D levels, whereas genetically reduced high-density lipoprotein-cholesterol is not associated with low 25(OH)D levels. These findings suggest that low 25(OH)D levels observationally is simply a marker for elevated atherogenic lipoproteins and question a role for vitamin D supplementation in the prevention of cardiovascular disease.
authors: From the Department of Clinical Biochemistry (E.M.O., S.A., B.G.N.), The Copenhagen General Population Study (E.M.O., S.A., B.G.N.), Herlev Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (S.A., B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark (B.G.N.); and School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (E.M.O.).
authors: Esther M
authors: EM
authors: Ooi
authors: From the Department of Clinical Biochemistry (E.M.O., S.A., B.G.N.), The Copenhagen General Population Study (E.M.O., S.A., B.G.N.), Herlev Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (S.A., B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark (B.G.N.); and School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (E.M.O.).
authors: Shoaib
authors: S
authors: Afzal
authors: From the Department of Clinical Biochemistry (E.M.O., S.A., B.G.N.), The Copenhagen General Population Study (E.M.O., S.A., B.G.N.), Herlev Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (S.A., B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark (B.G.N.); and School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (E.M.O.). Boerge.Nordestgaard@regionh.dk.
authors: Børge G
authors: BG
authors: Nordestgaard
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000235:genetics*; D002784:Cholesterol / Q000097:blood*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003627:Data Interpretation, Statistical; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011897:Random Allocation; D012307:Risk Factors; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014807:Vitamin D; D002784:Cholesterol; C104450:25-hydroxyvitamin D
keywords: Mendelian randomization analysis risk factors; genetics; vitamin D