Skip to main content
SpringerLink
Log in

Polymorphic markers of the NO synthase genes and genetic predisposition to diabetic polyneuropathy in type 1 diabetes mellitus

  • Genomics. Transcriptomics. Proteomics
  • Published:
Molecular Biology Aims and scope Submit manuscript

Abstract

The allele and genotype frequency distributions of polymorphic markers of the NOS1, NOS2, and NOS3 genes coding for three different NO synthases were compared for type 1 diabetes mellitus (T1DM) patients with or without diabetic polyneuropathy (DPN). The groups (total 180 patients, ethnic Russians or East Slavs from Moscow) had nonoverlapping (polar) phenotypes. Group DPN+ included patients with DPN and T1DM duration of no more than 5 years. Control group DPN- included patients without DPN and with T1DM duration of at least 10 years. No significant differences in allele and genotype frequency distributions were revealed for the polymorphic markers (CA) n of gene NOS1 (CCTTT) n of gene NOS2, and ecNOS4a/4b and Glu298Asp of gene NOS3, suggesting a lack of association between the polymorphic markers and DPN. In the case of the (CCTTT) n polymorphic marker of the NOS2 gene, a tendency toward an association with DPN was observed for allele 14. Carriers of this allele have a lower risk of DPN in T1DM.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Balabolkin M.I., Klebanova E.M., Kreminskaya V.M. 2001. Pathogenesis of angiopathies in diabetes mellitus. Sakharn. Diabet. 1, 5–11

    Google Scholar 

  2. Brownlee M. 2001. Biochemistry and molecular cell biology of diabetic complications. Nature. 414, 813–820.

    Article  CAS  PubMed  Google Scholar 

  3. Palmer R.M.J., Ferrige A.G., Moncada S. 1987. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 327, 524–526.

    Article  CAS  PubMed  Google Scholar 

  4. Moncada S., Palmer R.M., Higgs E.A. 1991. Nitric oxide: Physiology, pathophysiology and pharmacology. Pharmacol. Rev. 43, 109–142.

    CAS  PubMed  Google Scholar 

  5. Cooke J.P., Tsao P. 1993. Cytoprotective effects of nitric oxide. Circulation. 88, 2451–2454.

    CAS  PubMed  Google Scholar 

  6. Palmer R.M.J., Rees D.D., Ashton D.S., Moncada S. 1988. L-Arginine is the physiological precursor for the formation of nitric oxide in endothelium-dependent relaxation. Biochem. Biophys. Res. Commun. 153, 1251–1256.

    CAS  PubMed  Google Scholar 

  7. Knowles R.G., Moncada S. 1994. Nitric oxide synthases in mammals. Biochem J. 298, 249–258.

    CAS  PubMed  Google Scholar 

  8. Hattori R., Sase K., Eizawa H., et al. 1994. Structure and function of nitric oxide synthases. Int. J. Cardiol. 47, 71–75.

    Article  PubMed  Google Scholar 

  9. Marsden P.A., Heng H.H.Q., Scherer S.W., et al. 1993. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J. Biol. Chem. 268, 17478–17488.

    CAS  PubMed  Google Scholar 

  10. Xu W., Gorman P., Sheer D., et al. 1993. Regional localization of gene coding for human neuronal nitric oxide synthase (NOS1) to 12q24.2–24.31 by fluorescent in situ hybridization. Cytogenet. Cell Genet. 64, 62–63.

    CAS  PubMed  Google Scholar 

  11. Hall A.V., Antoniou H., Wang Y., et al. 1994. Structural organization of human neuronal nitric oxide synthase gene (NOS1). J. Biol. Chem. 269, 33082–33090.

    CAS  PubMed  Google Scholar 

  12. Grasemann H., Dazen J. M., Deykin A., et al. 1999. Simple tandem repeat polymorphisms in neuronal nitric oxide synthase gene in different ethnic populations. Hum. Hered. 49, 139–141.

    Article  CAS  PubMed  Google Scholar 

  13. Grasemann H., Yandava C.H., Storm van’s Gravesande K., et al. 2000. A neuronal NO synthase (NOS1) gene polymorphism is associated with asthma. Biochem. Biophys. Res. Commun. 272, 391–394.

    Article  CAS  PubMed  Google Scholar 

  14. Marsden P.A., Heng H.H.Q., Duff C.L., et al. 1994. Localization of the human gene for inducible nitric oxide synthase (NOS2) to chromosome 17q11.2–q12. Genomics. 19, 183–185.

    Article  CAS  PubMed  Google Scholar 

  15. Chartrain N.A., Geller D.A., Koty P.P., et al. 1994. Molecular cloning, structure and chromosomal localization of the human inducible nitric oxide synthase gene. J. Biol. Chem. 269, 6765–6772.

    CAS  PubMed  Google Scholar 

  16. Xu W., Liu L., Empson P.C., et al. 1997. Evolution of a homopurine-homopyrimidine pentanucleotide repeat sequence upstream of the human inducible nitric oxide synthase gene. Gene. 204, 165–170.

    Article  CAS  PubMed  Google Scholar 

  17. Warpeha K.M., Xu W., Liu L., et al. 1999. Genotyping and functional analysis of a polymorphic (CCTTT)n repeat of NOS2A in diabetic retinopathy. FASEB J. 13, 1825–1832.

    CAS  PubMed  Google Scholar 

  18. Johannesen J., Tarnow L., Parving H-H., et al. 2000. CCTTT-Repeat polymorphysim in the human NOS2-promoter confers low risk of diabetic nephropathy in type 1 diabetic patients. Diabetes Care. 23, 560–562.

    CAS  PubMed  Google Scholar 

  19. Robinson L.J., Weremowicz S., Morton C.C., Michel T. 1994. Isolation and chromosomal localization of human endothelial nitric oxide synthase (NOS3) gene. Genomics. 19, 350–357.

    Article  CAS  PubMed  Google Scholar 

  20. Marsden P.A., Heng H.H.Q., Scherer S.W., et al. 1993. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J. Biol. Chem. 268, 17478–17488.

    CAS  PubMed  Google Scholar 

  21. Miyahara K., Kawamoto T., Sase K., et al. 1994. Cloning and structural characterization of the human endothelial nitric-oxide-synthase gene. Eur. J. Biochem. 223, 719–726.

    Article  CAS  PubMed  Google Scholar 

  22. Shimasaki Y., Yasue H., Yoshimura M., et al. 1998. Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction. J. Am. Coll. Cardiol. 31, 1506–1510.

    CAS  PubMed  Google Scholar 

  23. Tsukada T., Yokoyama K., Arai T., et al. 1998. Evidence of association of the ecNOS gene polymorphism with plasma NO metabolite levels in humans. Biochem. Biophys. Res. Commun. 245, 190–193.

    CAS  PubMed  Google Scholar 

  24. Wang X.L., Mahaney M.C., Sim A.S., et al. 1997. Genetic contribution of the endothelial constitutive nitric oxide synthase gene to plasma nitric oxide levels. Arterioscler. Thromb. Vasc. Biol. 17, 3147–3153.

    CAS  PubMed  Google Scholar 

  25. Adachi T., Wang X.L. 1998. Association of extracellular-superoxide dismutase phenotype with the endothelial constitutive nitric oxide synthase polymorphism. FEBS Lett. 433, 166–168.

    CAS  PubMed  Google Scholar 

  26. Voron’ko O.E., Chistyakov D.A., Shestakova M.V., et al. 1999. Polymorphism of endothelial NO synthase gene and genetic predisposition to nephropathy in insulin-independent diabetes mellitus. Sakharn. Diabet. 2, 2–3.

    Google Scholar 

  27. Zanchi A., Moczulski D.K., Hanna L.S., et al. 2000. Risk of advanced diabetic nephropathy in type 1 diabetes is associated with endothelial nitric oxide synthase gene polymorphism. Kidney Int. 57, 405–413.

    CAS  PubMed  Google Scholar 

  28. Strokov I.A., Novosadova M.V., Barinov A.N., Yakhno N.N. 2000. Clinical methods for estimating the severity of diabetic polyneuropathy. Nevrol. Zh. 5, 14–18.

    Google Scholar 

  29. Dyck P.J., Melton J.L., O’Brien P.C., Service F.G. 1997. Approaches to improve epidemiological studies of diabetic neuropathy: Insights from the Rochester Diabetic Neuropathy Study. Diabetes. 46, 5–8.

    Google Scholar 

  30. Komantsev V.N., Sabolotnykh V.A. 2001. Metodicheskie osnovy klinicheskoi elektroneiromiografii. Rukovodstvo dlya vrachei (Methodological Basis of Clinical Electroneuromyography: A Manual for Physicians). St. Petersburg.

  31. Budowle B., Baechtel F.S. 1990. Modifications to improve the effectiveness of resrtiction fragment length polymorphism. Appl. Electrophor. 1, 181–187.

    CAS  Google Scholar 

  32. Hutchon D. http://Calculator for confidence intervals for odds ratio unmatched case control study.htm

  33. Stockle J.-C., Muller B., Andiantsitokhoina R., Kleshchev A. 1998. Nitric oxide hyperproduction in vascular pathophysiology. Biokhimiya 63, 976–983.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. State Research Center GosNIIGenetika, Moscow, 117545, Russia

    E. V. Zotova, O. E. Voron’ko & V. V. Nosikov

  2. Department of Endocrinology and Diabetology, Russian Medical Academy of Postgraduate Education, WHO Center of Informatics in Diabetes, Moscow, 125315, Russia

    T. R. Bursa, I. V. Galeev & I. A. Strokov

Authors
  1. E. V. Zotova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. O. E. Voron’ko
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T. R. Bursa
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. V. Galeev
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. I. A. Strokov
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. V. Nosikov
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

__________

Translated from Molekulyarnaya Biologiya, Vol. 39, No. 2, 2005, pp. 224–229.

Original Russian Text Copyright © 2005 by Zotova, Voron’ko, Bursa, Galeev, Strokov, Nosikov.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zotova, E.V., Voron’ko, O.E., Bursa, T.R. et al. Polymorphic markers of the NO synthase genes and genetic predisposition to diabetic polyneuropathy in type 1 diabetes mellitus. Mol Biol 39, 200–205 (2005). https://doi.org/10.1007/s11008-005-0029-5

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11008-005-0029-5

Key words

Search

Navigation