title: Sequence variation in vitamin K epoxide reductase gene is associated with survival and progressive coronary calcification in chronic kidney disease.
abstract: OBJECTIVE
  Sequence variations in the gene(s) encoding vitamin K epoxide reductase complex subunit 1 (VKORC1), the enzyme target of warfarin, have been associated with increased cardiovascular disease in the general population. Coronary artery calcification (CAC) is a prevalent form of cardiovascular disease in chronic kidney disease. We tested the hypothesis that the VKORC1 rs8050894 CC genotype would be associated with mortality and progression of CAC ≤ 4 years.
  
  
  RESULTS
  This study is an observational, prospective study of 167 individuals with stages 3 to 5 chronic kidney disease. Survival ≤ 4 years was assessed in all participants, and CAC progression was measured in a subset of 86 patients. Participants with the CG/GG genotype of VKORC1 had higher baseline CAC scores (median score, 112 versus 299; P=0.036). Of those 86 patients who had a 4-year CAC score, those with the CG/GG genotype had an increased risk of progressive CAC (adjusted for age, diabetes mellitus, estimated glomerular filtration rate, and hypertension) compared with those with the CC genotype. Four-year mortality risk was 4 times higher for individuals with the CG/GG genotypes compared with individuals with the CC genotype (odds ratio, 3.8; 95% confidence interval, 1.2-12.5; P=0.02), adjusted for age, sex, diabetes mellitus, estimated glomerular filtration rate, baseline CAC, and hypertension.
  
  
  CONCLUSIONS
  Patients with the CG/GG genotype of VKORC1 had a higher risk of CAC progression and a poorer survival. These data provide new perspectives on the potential extrahepatic role of VKORC1 in individuals with chronic kidney disease.
authors.affiliation: From the Medicine (R.M.H., A.T., P.D.J., A.R.M., J.S.G.) and Radiology (R.L.N.), Queen's University, Kingston, Ontario, Canada; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA (S.L.B.); and Clinical Research Centre, Kingston General Hospital, Kingston, Ontario, Canada (W.M.H.). holdenr@kgh.kari.net.
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Holden
authors.affiliation: From the Medicine (R.M.H., A.T., P.D.J., A.R.M., J.S.G.) and Radiology (R.L.N.), Queen's University, Kingston, Ontario, Canada; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA (S.L.B.); and Clinical Research Centre, Kingston General Hospital, Kingston, Ontario, Canada (W.M.H.).
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Booth
authors.affiliation: From the Medicine (R.M.H., A.T., P.D.J., A.R.M., J.S.G.) and Radiology (R.L.N.), Queen's University, Kingston, Ontario, Canada; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA (S.L.B.); and Clinical Research Centre, Kingston General Hospital, Kingston, Ontario, Canada (W.M.H.).
authors.forename: Angie
authors.initials: A
authors.lastname: Tuttle
authors.affiliation: From the Medicine (R.M.H., A.T., P.D.J., A.R.M., J.S.G.) and Radiology (R.L.N.), Queen's University, Kingston, Ontario, Canada; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA (S.L.B.); and Clinical Research Centre, Kingston General Hospital, Kingston, Ontario, Canada (W.M.H.).
authors.forename: Paula D
authors.initials: PD
authors.lastname: James
authors.affiliation: From the Medicine (R.M.H., A.T., P.D.J., A.R.M., J.S.G.) and Radiology (R.L.N.), Queen's University, Kingston, Ontario, Canada; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA (S.L.B.); and Clinical Research Centre, Kingston General Hospital, Kingston, Ontario, Canada (W.M.H.).
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Morton
authors.affiliation: From the Medicine (R.M.H., A.T., P.D.J., A.R.M., J.S.G.) and Radiology (R.L.N.), Queen's University, Kingston, Ontario, Canada; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA (S.L.B.); and Clinical Research Centre, Kingston General Hospital, Kingston, Ontario, Canada (W.M.H.).
authors.forename: Wilma M
authors.initials: WM
authors.lastname: Hopman
authors.affiliation: From the Medicine (R.M.H., A.T., P.D.J., A.R.M., J.S.G.) and Radiology (R.L.N.), Queen's University, Kingston, Ontario, Canada; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA (S.L.B.); and Clinical Research Centre, Kingston General Hospital, Kingston, Ontario, Canada (W.M.H.).
authors.forename: Robert Louis
authors.initials: RL
authors.lastname: Nolan
authors.affiliation: From the Medicine (R.M.H., A.T., P.D.J., A.R.M., J.S.G.) and Radiology (R.L.N.), Queen's University, Kingston, Ontario, Canada; Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA (S.L.B.); and Clinical Research Centre, Kingston General Hospital, Kingston, Ontario, Canada (W.M.H.).
authors.forename: Jocelyn S
authors.initials: JS
authors.lastname: Garland
mesh_terms: D000328:Adult; D000368:Aged; D003324:Coronary Artery Disease / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D011446:Prospective Studies; D051436:Renal Insufficiency, Chronic / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D061205:Vascular Calcification / Q000201:enzymology / Q000235:genetics* / Q000401:mortality; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*
chemical_list: C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: mortality; renal insufficiency, chronic; vitamin K; vitamin K epoxide reductases