The K121Q polymorphism of ENPP1 and peripheral arterial disease

Heart Vessels. 2008 Mar;23(2):104-7. doi: 10.1007/s00380-007-1014-9. Epub 2008 Apr 4.


The K121Q variant of the ectonucleotide pyrophosphatase/ phosphodiesterase 1 (ENPP1) gene is associated with obesity, insulin resistance, and early myocardial infarction. Therefore, we hypothesized that the K121Q polymorphism might also be associated with an increased risk for peripheral arterial disease. Four hundred patients with peripheral arterial disease and 400 controls matched for sex and age (+/- 2 years) were genotyped cross-sectionally for the K121Q single nucleotide polymorphism of the ENPP1 gene. The frequency for the 121Q allele was 0.25 both in patients with peripheral arterial disease and in controls (P = 0.75). Subgroup analysis revealed association of the ENPP1 121QQ genotype with higher glycohemoglobin A1C levels (P = 0.001) and earlier onset of peripheral arterial disease (P = 0.003) in the cohort of nonsmokers. Whereas the K121Q genotype of the ENPP1 gene is not associated with presence of peripheral arterial disease in the whole Linz Peripheral Arterial Disease population, it is associated with type 2 diabetes mellitus and earlier onset of peripheral arterial disease in the subgroup of nonsmoking patients.

MeSH terms

  • Aged
  • Case-Control Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Glycated Hemoglobin A / analysis
  • Humans
  • Male
  • Middle Aged
  • Peripheral Vascular Diseases / enzymology
  • Peripheral Vascular Diseases / genetics*
  • Phosphoric Diester Hydrolases / genetics*
  • Polymorphism, Single Nucleotide*
  • Pyrophosphatases / genetics*
  • Risk Factors
  • Smoking / adverse effects


  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • Phosphoric Diester Hydrolases
  • ectonucleotide pyrophosphatase phosphodiesterase 1
  • Pyrophosphatases