Advertisement

Heart and Vessels

, Volume 23, Issue 2, pp 104–107 | Cite as

The K121Q polymorphism of ENPP1 and peripheral arterial disease

  • Philipp EllerEmail author
  • Wilfried Schgoer
  • Thomas Mueller
  • Ivan Tancevski
  • Egon Demetz
  • Kristina Duwensee
  • Andreas Ritsch
  • Meinhard Haltmayer
  • Josef R. Patsch
Original Article

Abstract

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.

Key words

ENPP1 Peripheral arterial disease K121Q polymorphism 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Giachelli CM, Speer MY, Li X, Rajachar RM, Yang H (2005) Regulation of vascular calcification: roles of phosphate and osteopontin. Circ Res 96:717–722PubMedCrossRefGoogle Scholar
  2. 2.
    Johnson K, Polewski M, van Etten D, Terkeltaub R (2005) Chondrogenesis mediated by PPi depletion promotes spontaneous aortic calcification in NPP1-/-mice. Arterioscler Thromb Vasc Biol 25:686–691PubMedCrossRefGoogle Scholar
  3. 3.
    Buckley MF, Loveland KA, McKinstry WJ, Garson OM, Goding JW (1990) Plasma cell membrane glycoprotein PC-1. cDNA cloning of the human molecule, amino acid sequence, and chromosomal location. J Biol Chem 265:17506–17511PubMedGoogle Scholar
  4. 4.
    Okawa A, Nakamura I, Goto S, Moriya H, Nakamura Y, Ikegawa S (1998) Mutation in Npps in a mouse model of ossification of the posterior longitudinal ligament of the spine. Nat Genet 19:271–273PubMedCrossRefGoogle Scholar
  5. 5.
    Abate N, Chandalia M, Satija P, Adams-Huet B, Grundy SM, Sandeep S, Radha V, Deepa R, Mohan V (2005) ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes. Diabetes 54:1207–1213PubMedCrossRefGoogle Scholar
  6. 6.
    Bacci S, Ludovico O, Prudente S, Zhang YY, Di Paola R, Mangiacotti D, Rauseo A, Nolan D, Duffy J, Fini G, Salvemini L, Amico C, Vigna C, Pellegrini F, Menzaghi C, Doria A, Trischitta V (2005) The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction. Diabetes 54:3021–3025PubMedCrossRefGoogle Scholar
  7. 7.
    Maddux BA, Sbraccia P, Kumakura S, Sasson S, Youngren J, Fisher A, Spencer S, Grupe A, Henzel W, Stewart TA, et al. (1995) Membrane glycoprotein PC-1 and insulin resistance in noninsulin-dependent diabetes mellitus. Nature 373:448–451PubMedCrossRefGoogle Scholar
  8. 8.
    Meyre D, Bouatia-Naji N, Tounian A, Samson C, Lecoeur C, Vatin V, Ghoussaini M, Wachter C, Hercberg S, Charpentier G, Patsch W, Pattou F, Charles MA, Tounian P, Clement K, Jouret B, Weill J, Maddux BA, Goldfine ID, Walley A, Boutin P, Dina C, Froguel P (2005) Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes. Nat Genet 37:863–867PubMedCrossRefGoogle Scholar
  9. 9.
    Costanzo BV, Trischitta V, Di Paola R, Spampinato D, Pizzuti A, Vigneri R, Frittitta L (2001) The Q allele variant (GLN121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (LYS121). Diabetes 50:831–836PubMedCrossRefGoogle Scholar
  10. 10.
    Canani LH, Ng DP, Smiles A, Rogus JJ, Warram JH, Krolewski AS (2002) Polymorphism in ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene (ENPP1/PC-1) and early development of advanced diabetic nephropathy in type 1 diabetes. Diabetes 51:1188–1193PubMedCrossRefGoogle Scholar
  11. 11.
    Endler G, Mannhalter C, Sunder-Plassmann H, Schillinger M, Klimesch A, Exner M, Kapiotis S, Meier S, Kunz F, Raiger E, Huber K, Wagner O, Sunder-Plassmann R (2002) The K121Q polymorphism in the plasma cell membrane glycoprotein 1 gene predisposes to early myocardial infarction. J Mol Med 80:791–795PubMedCrossRefGoogle Scholar
  12. 12.
    Mueller T, Marschon R, Dieplinger B, Haidinger D, Gegenhuber A, Poelz W, Webersinke G, Haltmayer M (2005) Factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations are not associated with chronic limb ischemia: the Linz Peripheral Arterial Disease (LIPAD) study. J Vasc Surg 41:808–815PubMedCrossRefGoogle Scholar
  13. 13.
    Lin J, Chen B, Wang JH, Zeng MS, Wang YX (2006) Whole-body three-dimensional contrast-enhanced magnetic resonance (MR) angiography with parallel imaging techniques on a multichannel MR system for the detection of various systemic arterial diseases. Heart Vessels 21:395–398PubMedCrossRefGoogle Scholar
  14. 14.
    Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, Jones DN (1997) Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg 26:517–538PubMedCrossRefGoogle Scholar
  15. 15.
    Abate N, Carulli L, Cabo-Chan A, Jr., Chandalia M, Snell PG, Grundy SM (2003) Genetic polymorphism PC-1 K121Q and ethnic susceptibility to insulin resistance. J Clin Endocrinol Metab 88:5927–5934PubMedCrossRefGoogle Scholar
  16. 16.
    Laukkanen O, Pihlajamaki J, Lindstrom J, Eriksson J, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Tuomilehto J, Uusitupa M, Laakso M (2004) Common polymorphisms in the genes regulating the early insulin signalling pathway: effects on weight change and the conversion from impaired glucose tolerance to Type 2 diabetes. The Finnish Diabetes Prevention Study. Diabetologia 47:871–877PubMedCrossRefGoogle Scholar
  17. 17.
    Faxon DP, Fuster V, Libby P, Beckman JA, Hiatt WR, Thompson RW, Topper JN, Annex BH, Rundback JH, Fabunmi RP, Robertson RM, Loscalzo J (2004) Atherosclerotic Vascular Disease Conference: Writing Group III: pathophysiology. Circulation 109:2617–2625PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2008

Authors and Affiliations

  • Philipp Eller
    • 1
    Email author
  • Wilfried Schgoer
    • 1
  • Thomas Mueller
    • 2
  • Ivan Tancevski
    • 1
  • Egon Demetz
    • 1
  • Kristina Duwensee
    • 1
  • Andreas Ritsch
    • 1
  • Meinhard Haltmayer
    • 2
  • Josef R. Patsch
    • 1
  1. 1.Department of Internal MedicineMedical University InnsbruckInnsbruckAustria
  2. 2.Department of Laboratory MedicineKonventhospital Barmherzige BruederLinzAustria

Personalised recommendations