Association of polymorphic markers of TNF, IL 6 and IL10 genes with the clinical and morphological features of chronic glomerulonephritis


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Abstract

Objective. To examine the association of polymorphic markers G(-238)A of TNF gene, G(-174)C of IL6 gene and G(-lO82)A of ILIO gene with the clinical and morphological features of chronic glomerulonephritis (CGN). Materials and methods. Clinical syndromes and morphological variants of nephritis regarding the carriage of polymorphic markers of tnf, IL6 and ILIO genes were retrospectively analyzed in 102 CGn patients (47 men and 55 women) the at the time of diagnosis. Results. Examination of clinical features of CGN, regarding the polymorphic marker G(-238)A of TNF gene did not reveal significant differences between treatment groups. Carriers of the с allele of IL6 gene compared with GG homozygotes more frequently had renal dysfunction (35.7% and і3%, respectively, p=0.014). There was a tendency to differences in the activity of CGN, depending on the polymorphic marker G(-174)C of IL6 gene: high activity of CGN (PU>3 g/day or NS with preserved renal function), p=0.088, was more frequently observed in patients with GG genotype, whereas carriers of с allele had higher rates of very active CGN (PU>3 g/day, or NS with concomitantly impaired renal function), p=0.069. Carriers of polymorphic marker genotype G(-lO82)A of ilio gene were more frequently found to have ah (56.3% compared with 32.2% of carriers g allele, respectively, p=0.023), and tended to more frequently have combination of NS and hypertension (29,7% vs. і5,5% in carriers of the g allele, respectively, p=0.082). The analysis of the association of polymorphic markers of tnf, IL6 and ILIO genes with morphological variants of CGN revealed a trend towards more frequent occurrence of proliferative CGN variants in patients with the GG genotype (Tnf gene) as compared with carriers of the a allele (46.3% and 20.0%, respectively, p=0.067), whereas in patients with genotype GG (IL6 gene) nonproliferative nephritis was more frequently (53.7%) found relative to carriers of с allele (26.7%); P = 0.067. Conclusion. There is association of polymorphic markers G(-174)C of IL6 gene and G(-i082)A of ILIO gene with clinical manifestation of CGN at the time of diagnosis. The carriage of allele с of polymorphic marker G(-174)C of IL6 gene is associated with more frequent renal impairment at the onset of CGn, and AA genotype of polymorphic marker G(-i082)A of ILIO gene - with developing hypertension.

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  1. Орлова Г.М., Матвеев В.Н., Козина О.А. Анализ регистра больных с хронической почечной недостаточностью в Прибайкалье. Нефрология и диализ. 2005; 7(3): 280.
  2. Stengel B., Billon S., van Dijk P., Jager K.J., Dekker F.W., Simpson K., Briggs J.D. Trends in the Incidence of Renal Replacement Therapy for EndStage Renal Disease in Europe, 1990-1999. Nephrol. Dial. Transplant. 2003; 18: 1824-1833.
  3. United States Renal Data System. Incidence and prevalence [Chapter 2]. Annual data report, 2006. Minneapolis, MN: USRDS Coordinating Center; 2006. Available at http://www.usrds.org/2006/pdf/02_incid_prev_06.pdf.
  4. Вашурина Т.В., Сергеева Т.В. Цитокины и адгезивные молекулы в патогенезе хронического гломерулонефрита. Нефрология и диализ. 2002; 3: 171-181.
  5. Богомазов С.Ю., Гладских О.П., Иванов А.А. и др. Цитокины и внеклеточный матрикс при экспериментальных гломерулопатиях. Арх. патологии. 1997; 59(6): 45-50.
  6. Chen A., Chen W.P., Sheu L.F., Lin C.Y. Pathogenesis of IgA nephropathy: in vitro activation of human mesangial cells by IgA immune complex leads to cytokine secretion. J. Pathol. 1994; 173(2): 119-126.
  7. Liang Y., Zhang J., Zhou Y., Xing G., Zhao G., Liu Z. Proliferation and Cytokine Production of Human Mesangial Cells Stimulated by Secretory IgA Isolated from Patients with IgA Nephropathy. Cell. Physiol. Biochem. 2015; 36(5): 1793-1808.
  8. Couser W.G. Pathogenesis of glomerular damage in glomerulonephritis. Nephrol. Dial. Transplant. 1998; 13: 10-15.
  9. Waldherr R., Noronha I.L., Niemir Z., Krüger C., Stein H., Stumm G. Expression of cytokines and growth factors in human glomerulonephritides. Pediatr. Nephrol. 1993; 7(4): 471-478.
  10. Ifuku M., Miyake K., Watanebe M., Ito K., Abe Y., Sasatomi Y., Ogahara S., Hisano S., Sato H., Saito T., Nakashima H. Various roles of Th cytokine mRNA expression in different forms of glomerulonephritis. Am. J. Nephrol. 2013; 38(2): 115-123.
  11. Чеботарева Н.В., Бобкова И.Н., Непринцева Н.В., Козловская Л.В., Малкандуева З.Т. Мочевые биомаркеры повреждения подоцитов: значение для оценки течения и прогноза хронического гломерулонефрита. Терапевтический архив. 2015; 6: 34-39.
  12. Чурносов М.И., Калмыкова Е.В., Некипелова Е.В., Рудых Н.А., Аристова И.К., Должиков А.А. Аллельные варианты генов интерлейкинов при хроническом гломерулонефрите. Цитокины и воспаление. 2010; 9(2): 37-41.
  13. Петросян Э.К., Цыгин А.Н., Шестаков А.Е., Носиков В.В. Роль генетического полиморфизма интерлейкинов 4 и 13 в развитии нефротического синдрома с минимальными изменениями у детей и подростков. Педиатрия. 2006; 5: 7-10.
  14. Tripathi G., Jafar T., Mahdal K., Mahdi A.A., Awasthi S., Sharma R.K., Kumar A., Gulati S., Agrawal S. Does cytokines gene polymorphism affect steroid responses in idiopathic nephritic syndrome? Indian J. Med. Sci. 2008; 62: 383-391.
  15. Калмыкова Е.В., Полякова И.С., Прощаев К.И., Нестеров В.Г., Ващилин В.С., Чурносов М.И. Изучение взаимосвязей молекулярногенетических маркеров интерлейкинов с клиническим течением хронического гломерулонефрита. Вестник Российского университета дружбы народов. Серия: Медицина. 2009; 4: 619-620.
  16. Parry R.G., Gillespie K.M., Parhnam A., Clark A.G., Mathieson P.W. Interleukin-4 and interleikin-4 receptor polymorphism in minimal change nephropathy. Clin. Sci. 1999; 96: 665-668.
  17. Vázquez-Huerta D.I., Alvarez-Rodnguez B.A., Topete-Reyes J.F., Muñoz-Valle J.F., Parra-Michel R., Fuentes-Ramirez F., Salazar-López M.A., Valle Y., Reyes-Castillo Z., Cruz-Gonzalez A., Brennan-Bourdon L.M., Torres-Carrillo N. Tumor necrosis factor alpha -238 G/A and -308 G/A polymorphisms and soluble TNF-a levels in chronic kidney disease: correlation with clinical variables. Int. J. Clin. Exp. Med. 2014; 7(8): 2111-2119.
  18. Amoli M.M., Martin J., Miranda-Filloy J.A., Garcia-Porrua C., Oilier W.E., Gonzalez-Gay M.A. Lack of association between interleukin-6 promoter polymorphism at position -174 and Henoch-Schönlein purpura. Clin. Exp. Rheumatol. 2007; 25(1 Suppl 44): S6-9.
  19. Hajeer A.H., Hutchinson I.V. Influence of TNF alpha gene polymorphisms on TNF alpha production and disease. Hum. Immunol. 2001; 62: 1191-1199.
  20. Ranganath P., Tripathi G., Sharma R.K. et al. Role of non-HLA genetic variants in end-stage renal disease. Tissue Antigens. 2009; 74(2): 147-155.
  21. Nikolova P.N., Ivanova M.I., Mihailova S.M. et al. Cytokine gene polymorphism in kidney transplantation--impact of TGF-beta 1, TNF-alpha and IL-6 on graft outcome.Transpl. Immunol. 2008; 18(4): 344-348.
  22. Buraczynska M., Mierzicki P., Buraczynska K., Dragan M., Ksiazek A. Tumor necrosis factor-alpha gene polymorphism correlates with cardiovascular disease in patients with end-stage renal disease. Mol. Diagn. Ther. 2007; 11(4): 257-263.
  23. Brull D.J., Montgomery H.E., Sanders J., Dhamrait S., Luong L., Rumley A., Lowe G.D., Humphries S.E. Atherosclerosis and Lipoproteins Interleukin-6 Gene -174 G > C and -572 G > C Promoter Polymorphisms Are Strong Predictors of Plasma Interleukin-6 Levels After Coronary Artery Bypass Surgery. Arterioscler. Thromb. Vasc. Biol. 2001; 21: 1458-1463.
  24. Семенова Н.А., Рязанцева Н.В., Новицкий В.В., Бычков В.А., Чечина О.Е. Роль полиморфизма гена IL6 -174C/G в развитии хронической HCV-инфекции. Бюллетень сибирской медицины. 2010; 5: 93-97.
  25. Muller-Steinhardt M., Hartel C., Muller B., Kirchner H., Fricke L. The interleukin-6-174 promoter polymorphism is associated with long-term kidney allograft survival. Kidney Int. 2002; 62: 1824-1827.
  26. Chiappelli M., Tampieri C., Tumini E., Porcellini E., Caldarera C.M., Nanni S., Branzi A., Lio D., Caruso M., Hoffmann E., Caruso C., Licastro F. Interleukin-6 gene polymorphism is an independent risk factor for myocardial infarction in men. Int. J. Immunogenet. 2005; 32: 349-353.
  27. Sie M.P., Sayed-Tabatabaei F.A., Oei H.H., Uitterlinden A.G., Pols H.A., Hofman A., van Duijn C.M., Witteman J.C. Interleukin 6 -174 g/c promoter polymorphism and risk of coronary heart disease: results from the rotterdam study and a meta-analysis. Arterioscler. Thromb. Vasc. Biol. 2006; 26: 212-217.
  28. Losito A., Kalidas K., Santoni S., Jeffery S. Association of interleukin-6-174G/ C promoter polymorphism with hypertension and left ventricular hypertrophy in dialysis patients. Kidney Int. 2003; 64: 616-622.
  29. Del Prete G., De Carli M., Almerigogna F., Giudizi M.G., Biagiotti R., Romagnani S. Human IL-10 is produced by both Type 1 Helper (Th1) and Type 2 Helper (Th2) T cell clones and inhibits their antigen-specific proliferation and Cytokine Production. J. Immunol. 1993; 150: 353-360.
  30. Fiorentino D.F., Zlotnik A., Mosmann T.R., Howard M., O'Garra A. IL-10 inhibits cytokine production by activated macrophages. J. Immunol. 1991; 147: 3815-3822.
  31. Moore K.W., O’Garra A., de Waal Malefyt R., Vieira P., Mosmann T.R. Interleukin-10. Annu. Rev. Immunol. 1993; 1: 165-190.
  32. Turner D.M., Williams D.M., Sankaran D., Lazarus M., Sinnott P.J., Hutchinson I.V. An investigation of polymorphism in the interleukin-10 gene promoter. Eur. J. Immunogenet. 1997; 24: 1-8.
  33. Eskdale J., Gallagher G., Verweij C.L., Keijsers V., Westendorp R.G., Huizinga T.W. Interleukin 10 secretion in relation to human IL-10 locus haplotypes. Proc. Natl. Acad. Sci. U S A 1999; 95: 9465-9470.
  34. Girndt M., Ulrich C., Kaul H., Sester U., Sester M., Köhler H. Uremiaassociated immune defect: the IL-10-CRP axis. Kidney Int. Suppl. 2003; 84: S76-S79.

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