Association of thecomplex of polymorphic markers of ACE genes, aldosteronsynthetase and endothelial synthetase of nitric oxide withprogression of chronic glomerulonephritis


Aim. To study association of the complex of polymorphic markers of ACE genes (ACE complex), aldosteron synthetase gene (CYP11B2) and endothelial synthetase of nitric oxide (NOS3) with onset,
course and progression of chronic glomerulonephritis (CGN).
Material and methods. 117 CGN patients were examined. Genetic predisposition to CGN development was studied by comparison of distributions of alleles and genotypes of polymorphic markers of
genes ACE, CYP11B2 and NOS3 in CGN patients and controls (n = 80) free of renal diseases and
arterial hypertension (AH). The course of CGN was analysed with consideration of the following factors: AH severity, proteinuria persistence, nephritic level for 6 months and longer, immunosuppressive
therapy and response to it, therapy with ACE inhibitors and/or blockers of antiotensin II receptors
(ARB). CGN progression rate end point was doubling of initial blood creatinine level.
Results. Significant differences in the incidence of the above alleles and genotypes in the patients and
controls were not found. The patients were divided into two groups: group 1 consisted of 25 patients
carrying the combination of alleles D+C+4a, group 2 consisted of the rest 92 patients. The groups did
not differ by CGN course parameters, but renal survival was significantly lower in carriers of the allele
combination D+C+4a. Cox's mono- and multifactorial regression analysis has shown that carriage of
the allele combination D+C+4a is an independent risk factor of renal survival deterioration.
Conclusion. No association was detected between polymorphic markers of genes ACE, CYP11B2 and
NOS3 and onset of CGN. Carriage ofD+C+4a allele combination is an independent factor of risk for
fast progression of chronic renal failure.


  1. Rigat В., Hubert С, Alhenc-Gelas F. et al. An insertion/dele tion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.J. Clin. Invest. 1990; 86: 1343-1346.
  2. Zee R. Y. L., Lou Y, Griffiths L. R,, Morris B. J. Association a polymorphism of the angiotensin I converting enzyme ge with essential hypertension. Biochem. Biophys. Res. Commi 1992; 184: 9-15.
  3. Shunkert H., Riegger G. Association between a deletion po morphism of the angiotensin converting enzyme gene and ] ventricular hypertrophy. N. Engl. J. Med. 1994; 330: 163' 1638.
  4. Ludwig E., Cornell P. S., Anderson J. L. et al. Angiotens: converting enzyme gene polymorphism is associated with mj cardial infarction but not with development of coronary ster, sis. Circulation 1995; 91: 2120-2124.
  5. Marre M., Bemadet P., Gallois Y. et al. Relationships betwe angiotensin I converting enzyme gene polymorphism, plasi levels, and diabetic retinal and renal complication. Diabei 1994; 43: 384-388.
  6. Pei Y, Scholey J., Thai K. et al. Association of angiotensinog gene T235 variant with progression of immunoglobin A nep ropathy in Caucasian patients. J. Clin. Invest. 1997; 100 (< 814-820.
  7. Ong-Ajyooth S., Ong-Ajyooh L., Limmongkon A. et al. The re inangiotensin system gene polymorphisms and clinicopath logical correlations in IgA nephropathy. J. Med. Assoc. Th; 1999; 82 (7): 681-689.
  8. Takeda Y., Yoneda Т., Demura M. et al. Sodium-induced ca diac aldosterone synthesis causes cardiac hypertrophy. End crinology 2000; 141 (5): 1901-1904.
  9. Rocha R., Stier С. Т. Jr., Kifor I. et al. Aldosterone: a mediat of myocardial necrosis and renal arteriopathy. Endocrinoloi 2000; 141 (10): 3871-3878.
  10. Greene E. L., Kren S., Hostetter Т. Н. Role of aldosterone the remnant kidney model in the rat. J. Clin. Invest. 1996; 9 1063-1068.
  11. Rocha R., Chander P. N., Zuckerman A., Stier С. Т. Jr. Role aldosterone in renal vascular injury in stroke-prone hypertei sive rats. Hypertension 1999; 33 (pt II): 232-237.
  12. Clyne С D., Zhang Y., Slutsker L. et al. Angiotensin II ar potassium regulate human CYP11B2 transcription throug common cis-elements. Mol. Endocrinol. 1997; 11 (5): 638- 649.
  13. White P. C, Slutsker L. Haplotype analysis of CYP11B2. Er doer. Res. 1995; 21 (1-2): 437-442.
  14. Pojoga L., Gautier S., Blanc H. et al. Genetic determination ( plasma aldosterone levels in essential hypertension. Am. J. Hj pertens. 1998; 11 (7): 856-860.
  15. Tamaki S., Iwai N., Tsujita Y, Kinoshita M. Genetic polymoi phism of CYP11B2 gene and hypertension in Japanese. Hypei tension 1999; 33: 266-270.
  16. Kupari M., Hautanen A., Lankinen L. et al. Associations be tween human aldosterone synthase (CYP11B2) gene polymoi phisms and left ventricular size, mass, and function. Circula tion 1998; 97: 569-575.
  17. Lovati E., Richard A., Frey B. et al. Genetic polymorphisms с the renin-angiotensin-aldosterone system in end-stage rens disease. Kidney Int. 2001; 60: 46-54.
  18. Song J., Narita I., Goto S. et al. Gender specific association о aldosterone synthase gene polymorphism with renal survival ii patients with IgA nephropathy. J. Med. Genet. 2003; 40: 372- 376.
  19. Tsukada Т., Yokoyama K., Aral T. et al. Evidence of associa tion of the ecNOS gene polymorphism with plasma NO me tabolite levels in humans. Biochem. Biophys. Res. Commun 1998; 245: 190-193.
  20. Wang Y, Kikuchi S., Suzuki H. et al. Endothelial nitric oxidi synthase gene polymorphism in intron 4 affects the progressioi of renal failure in non-diabetic renal disease. Nephrol. Dial Transplant. 1999; 14: 2898-2902.
  21. Burg M., Menne J., Ostendorf T. et al. Gene-polymorphisms о angiotensin converting enzyme and endothelial nitric oxide synthase in patients with primary glomerulonephritis. Clin Nephrol. 1997; 48 (4): 205-211.
  22. Vasku A., Soucek M., Znojil V. et al. Angiotensin I-convertinj enzyme and angiotensinogen gene interaction and prediction of essential hypertension. Kidney Int. 1998; 53: 1479-1482.
  23. Tiret L., Bonnardeaux A., Poirier O. et al. Synergistic effects ol angiotensin-converting enzyme and angiotensin-II type I receptor gene polymorphisms on risk of myocardial infarction. Lancet 1994; 334: 910-913.
  24. Raij L., Baylis С Glomerular actions of nitric oxide. Kidney Int. 1995; 48: 20-32.



Abstract - 84


Article Metrics

Metrics Loading ...


  • There are currently no refbacks.

Copyright (c) 2003 Kamyshova E.S., Kutyrina I.M., Nosikov V.V., Shvetsov M.Y., Gorashko N.M., Ignatyev I.V., Voronko О.Е., Shilo V.Y., Alyaev Y.G., Shilov E.M.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Address of the Editorial Office:

  • Novij Zykovskij proezd, 3, 40, Moscow, 125167

Correspondence address:

  • Novoslobodskaya str 31c4., Moscow, 127005, Russian Federation

Managing Editor:


© 2018 "Consilium Medicum" Publishing house

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies