Association of VKORC1 -1639 G>A polymorphism with carotid intima-media thickness in type 2 diabetes mellitus

Diabetes Res Clin Pract. 2011 Nov;94(2):236-41. doi: 10.1016/j.diabres.2011.06.021. Epub 2011 Jul 20.

Abstract

Aims: 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.

MeSH terms

  • Aged
  • Analysis of Variance
  • Carotid Arteries / diagnostic imaging*
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / enzymology
  • Carotid Artery Diseases / genetics*
  • Case-Control Studies
  • Chi-Square Distribution
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetic Angiopathies / diagnostic imaging
  • Diabetic Angiopathies / enzymology
  • Diabetic Angiopathies / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Greece
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Mixed Function Oxygenases / genetics*
  • Odds Ratio
  • Phenotype
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Risk Assessment
  • Risk Factors
  • Tunica Intima / diagnostic imaging*
  • Tunica Media / diagnostic imaging*
  • Ultrasonography
  • Vascular Calcification / diagnostic imaging
  • Vascular Calcification / enzymology
  • Vascular Calcification / genetics*
  • Vitamin K Epoxide Reductases

Substances

  • Mixed Function Oxygenases
  • VKORC1 protein, human
  • Vitamin K Epoxide Reductases