title: Association of VKORC1 -1639 G>A polymorphism with carotid intima-media thickness in type 2 diabetes mellitus.
abstract: OBJECTIVE
  Media calcification is a predictor of cardiovascular mortality in type 2 diabetes mellitus (T2DM). Undercarboxylation of some vitamin K-dependent proteins, due to genetic polymorphisms of VKORC1, can lead to calcification. We examined a potential association between VKORC1 -1639 G>A polymorphism and T2DM and, also, the association of this polymorphism with carotid intima-media thickness (cIMT).
  
  
  METHODS
  VKORC1 -1639 G>A polymorphism was determined in 299 T2DM patients and 328 controls of Caucasian origin using PCR-RFLP. cIMT was measured in a subgroup of 118 T2DM patients.
  
  
  RESULTS
  The frequency of VKORC1 genotypes between diabetic and nondiabetic subjects differed significantly (p=0.01). VKORC1 genotype was associated with T2DM in an adjusted model (OR 1.36, p=0.009). A statistically significant difference was observed in the maximum value of cIMT among different genotypes. VKORC1 -1639 G>A polymorphism was an independent predictor of cIMT (p=0.029) after adjusting for established risk factors.
  
  
  CONCLUSIONS
  The association between VKORC1 -1639 G>A polymorphism and risk of T2DM could be due to the higher prevalence of calcification in T2DM patients. This is supported by the independent association between VKORC1 -1639 G>A polymorphism and maximum cIMT in T2DM patients which is likely due to atherosclerosis characterized by increased calcification.
authors.affiliation: Lab of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, 68100 Alexandroupolis, Greece. atavrid@med.duth.gr
authors.forename: Anna
authors.initials: A
authors.lastname: Tavridou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Petridis
authors.forename: Michail
authors.initials: M
authors.lastname: Vasileiadis
authors.forename: Georgia
authors.initials: G
authors.lastname: Ragia
authors.forename: Ioannis
authors.initials: I
authors.lastname: Heliopoulos
authors.forename: Vassileios
authors.initials: V
authors.lastname: Vargemezis
authors.forename: Vangelis G
authors.initials: VG
authors.lastname: Manolopoulos
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006115:Greece; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D017540:Tunica Media / Q000000981:diagnostic imaging*; D014463:Ultrasonography; D061205:Vascular Calcification / Q000000981:diagnostic imaging / Q000201:enzymology / Q000235:genetics*; D064417:Vitamin K Epoxide Reductases
chemical_list: D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases