Association of gene TP53 polymorphic marker Pro72Arg with clinical characteristics of chronic glomerulonephritis


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Aim. To study association of geneTP53 polymorphic marker Pro72Arg coding synthesis of p53 protein with onset, course and progress of chronic glomerulonephritis (CGN).
Material and methods. We examined 126 patients (63 males and 63 females, mean age 38.8±13.2 years) with CGN duration 13.0±9.1 years. When analyzing genetic predisposition to CGN, we compared incidence rate of alleles/genotypes of polymorphic marker Pro72Arg of gene TP53 in CGN patients and 69 controls free of renal disease. CGN clinical features were assessed retrospectively including analysis of nephritis onset, clinical and morphological variants. The course of CGN was analysed by changes in severity of hypertension, persistence of proteinuria > 3 g/day during 6 months and longer, conduction of immunosuppressive therapy and response to it. In analysis of progression rate, doubling of blood creatinine was considered as an end point. We used polymerase chain reaction with analysis of restriction fragment length for identification of alleles of Pro72Arg polymorphic marker of TP53 gene.
Results. Distribution of the genotypes of the above polymorphic marker in CGN patients and in controls did not significantly differ. Depending on Pro allele carriage, CGN patients were divided into two groups: Arg/Arg group (59 carriers of genotype Arg/Arg) and Pro group (63 patients with genotype Arg/ Pro and 4 with genotype Pro/Pro). Carriage of Pro allele of gene TP53 was associated with high CGN activity at onset, presence of arteriolosclerosis and IgA deposits in kidney biopsy. Patients with genotype Arg/Arg more frequently developed nephritic syndrome without renal dysfunction syndrome.
Conclusion. We have discovered association of geneTP53 polymorphic marker Pro72Arg with clinical manifestations of CGN. Carriers of Pro allele more often have signs of active glomerular inflammation and vascular impairment with renal dysfunction while carriers of Arg/Arg genotype more frequently demonstrate isolated nephritic syndrome.

About the authors

Elena Sergeevna Kamyshova

Email: kamyshovaes@yandex.ru

Mikhail Yur'evich Shvetsov

Email: mshetsov@yandex.ru

Aleksey Evgen'evich Shestakov

Email: fimed-pcr@ mail.ru

Irina Mikhaylovna Kutyrina

Valeriy Vyacheslavovich Nosikov

E S Kamyshova

I.M. Sechenov First Moscow State Medical University, Moscow

I.M. Sechenov First Moscow State Medical University, Moscow

M Yu Shvetsov

I.M. Sechenov First Moscow State Medical University, Moscow

I.M. Sechenov First Moscow State Medical University, Moscow

A E Shestakov

Clinicodiagnostic Laboratory FimedLab, Moscow

Clinicodiagnostic Laboratory FimedLab, Moscow

I M Kutyrina

I.M. Sechenov First Moscow State Medical University, Moscow

I.M. Sechenov First Moscow State Medical University, Moscow

V V Nosikov

State Research Center "GosNIIgenetica", Moscow

State Research Center "GosNIIgenetica", Moscow

References

  1. Hunley T. E., Julian B. A., Phillips J. A. et al. Angiotensin converting enzyme gene polymorphism: potential silencer motif and impact on progression in IgA nephropathy. Kidney Int. 1996; 49: 571-577.
  2. Lovati E., Richard A., Frey B. et al. Genetic polymorphisms of the renin-angiotensin-aldosterone system in end-stage renal disease. Kidney Int. 2001; 60: 46-54.
  3. Wang Y., Kikuchi S., Suzuki H. et al. Endothelial nitric oxide synthase gene polymorphism in intron 4 affects the progression of renal failure in non-diabetic renal disease. Nephrol. Dial. Transplant. 1999; 14: 2898-2902.
  4. Song J., Narita I., Goto S. et al. Gender specific association of aldosterone synthase gene polymorphism with renal survival in patients with IgA nephropathy. J. Med. Genet. 2003; 40: 372- 376.
  5. Камышова Е. С., Кутырина И. М., Носиков В. В. и др. Ассоциация комплекса полиморфных маркеров генов ангиотензинпревращающего фермента, синтетазы альдостерона и эндотелиальной синтетазы оксида азота с прогрессированием хронического гломерулонефрита. Тер. арх. 2004; 9: 16-20.
  6. Камышова Е. С., Кутырина И. М., Носиков В. В., Швецов М. Ю. Значение полиморфных маркеров генов вазоактивных гормонов в оценке клинических особенностей хронического гломерулонефрита. Тер. арх. 2005; 6: 16-20.
  7. Kestila M., Lenkkeri U., Mannikko M. et al. Positionally cloned gene for a novel glomerular protein - nephrin - is mutated in congenital nephritic syndrome. Mol.Cell. Biol. 1998; 1 (4): 575-582.
  8. Tsukaguchi H., Sudbakar A., Cam Le T. et al. NPHS2 mutation in late-onset focal segmental glomerulosclerosis: R229Q is common disease-associated allele. J. Clin. Invest. 2002; 110 (11): 1659-1666.
  9. Pereira A. C., Pereira A. B., Mota G. F. et al. NPHS2 R229Q functional variant is associated with microalbuminuria in the general population. Kidney Int. 2004; 65: 1026-1030.
  10. Ruf R. G., Lichtenberger A., Karle S. M. et al. Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephritic syndrome. J. Am. Soc. Nephrol. 2004; 15: 722-732.
  11. Петросян Э. К., Белянская Т. В., Ильенко Л. И. и др. Полиморфный маркер 4G/5G гена PAI-1 у детей с хроническим гломерулонефритом. Нефрология 2006; 10 (4): 56- 61.
  12. Боброва Л. А., Козловская Н. Л., Шкарупо В. В. и др. Влияние генетической формы тромбофилии на клинико-морфологические проявления и характер течения хронического гломерулонефрита. Нефрология и диализ 2010; 12 (1): 25-33.
  13. Harrison D. J. Cell death in the diseased glomerulus. Histopathology 1988; 12: 679-683.
  14. Shimizu A., Kitamura H., Masuda Y. et al. Apoptosis in the repair process of experimental proliferative glomerulonephritis. Kidney Int. 1995; 47: 114-121.
  15. Shimizu A., Kitamura H., Masuda Y. Rare glomerular capillary regeneration and subsequent capillary regression with endothelial cell apoptosis in progressive glomerulonephritis. Am. J. Pathol. 1997; 151 (5): 1231-1239.
  16. Hamada T., Sasaguri T., Tanimoto A. Apoptosis of human kidney 293 cells is promoted by polymerized cadmium-metallothionein. Biophys. Res. Commun. 1996; 3: 829-834.
  17. Новожилова А. П., Плужников Н. Н., Новиков В. С. Механизмы клеточной гибели. В кн.: Новиков В. С. (ред.). Программированная клеточная смерть. СПб.: Наука; 1996. 9-29.
  18. Matlashewski G., Tuck D., Pim P. et al. Primary structure polymorphism at amino acide residue 72 of human p53. Mol. Cell. Biol. 1987; 7 (2): 961-963.
  19. Thomas M., Kalita A., Labrecque S. et al. Two polymorphic variants of wild type p53 differ biochemically and biologically. Mol. Cell. Biol. 1999; 19 (2): 1092-1100.
  20. Dumont P., Leu J. I., Delia Pietra A. C. et al. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat. Genet. 2003; 33: 357-365.
  21. Pim D., Banks L. P53 polymorphic variants at codon 72 exert different effects on cell cycle progression. Int. J. Cancer 2004; 108: 196-199.
  22. Chen R. H., Chang C. T., Wang T. Y. et al. p53 codon 72 proline/arginine polymorphism and autoimmune thyroid diseases. J. Clin. Lab. Anal. 2008; 22 (5): 321-326.
  23. Lee Y. H., Rho Y. H., Choi S. J et al. The functional p53 codon 72 polymorphism is associated with systemic lupus erythematosus. Lupus 2005; 14 (10): 842-845.
  24. Lee Y. H., Kim Y. R., Ji J. D. et al. p53 codon 72 polymorphism and rheumatoid arthritis. J. Rheumatol. 2001; 28 (11): 2392-2394.
  25. Macchioni P., Nicoli D., Casali B. et al. The codon 72 polymorphic variants of p53 in Italian rheumatoid arthritis patients. Clin. Exp. Rheumatol. 2007; 25 (3): 416-421.
  26. Moodley D., Mody G. M., Chuturgoon A. A. Functional analysis of the p53 codon 72 polymorphism in black South Africans with rheumatoid arthritis - a pilot study. Clinr. Rheumatol. 2010; 29 (10): 1099-1105.
  27. Петросян Э. К., Ильенко Л. И., Цыгин А. Н. и др. Влияние полиморфизма гена р53 на течение и исходы хронического гломерулонефрита у детей и подростков. Педиатрия 2006; 5: 4-7.
  28. Nakatsu T., Koike H., Han G. D. et al. Nephrin and podocin dissotiate at the onset of proteinuria n experimental membranous nephropathy. Kidney Int. 2005; 67: 2239-2253.
  29. Чеботарева Н. В., Бобкова И. Н., Козловская Л. В. Нефринурия как показатель структурно-функциональных нарушений гломерулярного фильтра у больных протеинурическими формами нефрита. Клин. нефрол. 2010; 4: 45-51.

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