Pharmacogenetic criteria for the efficacy of basic anti-inflammatory therapy for rheumatoid arthritis


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Abstract

Aim. To analyze the prognostic value of detection of allelic variants of the promoter regions of cytokine genes in patients with rheumatoid arthritis (RA) with varying efficiency of basic anti-inflammatory therapy (BAIT).
Subjects and methods. Eighty-nine patients with a valid diagnosis of RA, of them there were 79 females and 10 males (mean age 52.5±13.1 years), were examined. The patients received BAIT with methotrexate in a dose of 10.0-17.5 mg/week (77.5%) or with sulfasalazine in a dose of 2.0 g/day (22.5%) for 24 weeks. The efficiency of BAIT was evaluated using the European League Against Rheumatism (EULAR) criteria (DAS28) following 24 weeks. A high therapeutic effect was stated when DAS28 decreased by more than 1.2 scores. Changes in DAS28 by less than 0.6 scores were regarded as ineffective BAIT. Cytokine gene polymorphisms were studied by restriction analysis of amplification products. The following polymorphic sites in the interleukin genes: FNOA at positions C-863A, G-308A, G-238A, IL-1BT-31C, IL-4 C-590T, IL-6 G-174C, and IL-10 C-592A, were explored.
Results. The IL-6 G-174G genotype associated with the high production of this proinflammatory cytokine and the IL-IB C-31C genotype associated with the low production of interleukin-1в (IL-1в) were most frequently encountered in a group of patients with the high efficiency of BAIT (22 and 24.7%). At the same time the C allele associated with the low production of IL-6 and the IL1B T-31C genotype associated with the high production of this cytokine were most frequently detected at position of G-174C of the promoter regions in the IL-6 gene in patients unresponsive to BAIT (32 and 36%).
Conclusion. The allelic variants of the promoter regions of the IL-6 G-174G, IL-1B C-31C, IL-4 C-590T, and IL-10 C-592A can be genetically prognostic factors of formation of the high efficiency of BAIT.

About the authors

Vladimir Iosifovich Konenkov

Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Email: konenko@soramn.ru
лаборатория клинической иммуногенетики- д-р мед. наук, проф., акад. РАМН, зав. лаб. клинической иммуногенетики, дир. НИИКЭЛ СО РАМН, тел: 8-383-333-64-09; Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Elena Vladimirovna Zonova

Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

лаборатория клинической иммуногенетики- канд. мед. наук, зав. отд. терапии, клиника НИИКЭЛ СО РАМН, 8-383-332-29-59; Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Maksim Aleksandrovich Korolev

Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Email: kormax@bk.ru
лаборатория клинической иммуногенетики- канд. мед. наук, врач-ревматолог, зам. дир. НИИКЭЛ СО РАМН, 8-383-332-29-59; Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Yuliya Borisovna Leonova

Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Email: leobina@mail.ru
лаборатория клинической иммуногенетики- врач-терапевт, отд. терапии, клиника НИИКЭЛ СО РАМН, тел.: 8-383-332-29-59; Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Alla Vladimirovna Shevchenko

Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Email: shalla64@mail.ru
лаборатория клинической иммуногенетики- канд. мед. наук, ст. науч. сотр., лаб. клинической иммуногенетики8-382-227-01-96; Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Ol'ga Valer'evna Golovanova

Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Email: golovanova_olga@mail.ru
лаборатория клинической иммуногенетики- канд. биол. наук., ст. науч. сотр., лаб. клинической иммуногенетики, НИИКЭЛ СО РАМН, тел.: 8-383-227-01-96; Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Viktor Fedorovich Prokof'ev

Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

Email: vprok@ngs.ru
лаборатория клинической иммуногенетики- канд. мед. наук, вед. науч. сотр., лаб. клинической иммуногенетики, НИИКЭЛ СО РАМН, тел.: 8-383-227-01-96; Учреждение РАМН НИИ клинической и экспериментальной лимфологии Сибирского отделения РАМН

V I Konenkov

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

E V Zonova

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

M A Korolev

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

Yu B Leonova

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

A V Shevchenko

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

O V Golovanova

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

V F Prokofyev

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

Research Institute of Clinical and Experimental Lymphology, Siberian Branch, Russian Academy of Medical Sciences

References

  1. Seitz M., Wirthmьller U., Mцller B., Villiger P. M. The -308 tumour necrosis factor-alpha gene polymorphism predicts therapeutic response to TNF-alpha blockers in rheumatoid arthritis and spondyloarthritis patients. Rheumatology 2007; 46: 93- 96.
  2. O'Rielly D. D., Roslin N. M., Beyene J. et al. TNF-a1pha-308 G/A polymorphism and responsiveness to TNF-alpha blockade therapy in moderate to severe rheumatoid arthritis: a systematic review and meta-analysis. Pharmacogenom. J. 2009; 9: 161-167.
  3. Coenen M. J., Toonen E. J., Scheffer H. et al. Pharmacogenetics of anti-TNF treatment in patients with rheumatoid arthritis. Pharmacogenomics 2007; 8: 761-773.
  4. Kоненков B. И. Медицинская и экологическая иммуногенетика. Новосибирск: СО РАМН; 1999.
  5. Quinn M. A., Conaghan P. G., Emery P. The therapeutic approach of early intervention for rheumatoid arthritis: what is the evidence? Rheumatology (Oxford) 2001; 4: 1211-1220.
  6. Насонов Е. Л. Иммунопатология ревматических заболеваний. Инновационные технологии в диагностике и лечении ревматических заболеваний: Лекции цикла повышения квалификации врачей. М.; 2009.
  7. Fleischman R. M. Is there a need for new therapies for rheumatoid arthritis. J. Rheumatol. 2005; 32(73): 3-7.
  8. Goldblatt F., Isenberg D. A. New therapy for rheumatoid arthritis. Clin. Exp. Immunol. 2005; 140: 195-204.
  9. Wulk M. C., Furbun A., Metseluur H. J. et al. Are cytokine gene polymorphisms related to in vitro cytokine production profiles? Liver Transplant. 2003; 9(2): 170-171.
  10. Haukim N., Bidwell J. L., Smith A. J. P. et al. Cytokine gene polymorphism in human disease: on-line databases. Genes and Immunity 2002; 3: 313-330.
  11. Ranganathan P. An Update on Methotrexate pharmacogenetics in rheumatoid arthritis. Pharmacogenomics 2008; 9(4): 439-451.
  12. Arnett F. C., Edworthy S. M., Bloch D. et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthr. and Rheum. 1988; 31: 315-324.
  13. Steinbrocker O., Traeger C. N. Therapeutic criteria in rheumatoid arthritis. J. A. M. A. 1949; 40(8): 659-662.
  14. Fransen J., Creemers M. C., Van Riel P. L. Remission in rheumatoid arthritis: agreement of the disease activity score (DAS28) with the ARA preliminary remission criteria. Rheumatology (Oxford) 2004; 10: 1252-1255.
  15. Patino-Garcia A., Sotillo-Pineiro E., Modesto C., Sierrasesumaga L. Screening of the human tumor necrosis factor-alpha (TNF-alpha) gene promoter polymorphisms by PCR-DGGE analysis. Mutat. Res. 1999; 406: 121-125.
  16. Li H. Q., Li Z., Liu Y. et al. Association of polymorphism of tumor necrosis factor-alpha gene promoter region with outcome of hepatitis B virus infection. Wld J. Gastroenterol. 2005; 33: 5213-5217.
  17. Asghar T., Yoshida S., Kennedy S. et al. The tumor necrosis factor-a promoter-1031C polymorphism is associated with decreased risk of endometriosis in a Japanese population. Hum. Reprod. 2004; 11: 2509-2514.
  18. Zhang D., Zheng H., Zhou Y. et al. Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer. BMC Cancer 2007; 7: 45.
  19. Choi E., Lee H. J., Yoo T., Chanock S. A common haplotype of interleukin-4 gene IL-4 is associated with severe respiratory syncytial virus disease in Korean children. J. Infect. Dis. 2002; l86: 1207-1211.
  20. Fernandez-Real J.-M., Vendrell J., Richart C. et al. Platelet count and Interleukin-6 Gene polymorphism in healthy subjects. BMC Med. Genet. 2001; 2: 6.
  21. Mock C. C., Lanchbury J. S., Chan D. W., Lau C. S. Interleukin-10 promoter polymorphisms in Southern Chinese patients with systemic lupus erythematosus. Arthr. and Rheum. 1998; 41: 1090-1095.
  22. Вейр Б. Анализ генетических данных: Дискретные генетические признаки. М.: Медицина, 1995.
  23. Mehta C. R., Patel N. R., Gray R. On computing an exact confidence interval for the common odds ratio in several 2 Ѕ 2 contingency tables. J. Am. Stat. Assoc. 1985; 80: 969-973.
  24. Реброва О. Ю. Статистический анализ медицинских данных. Применение пакета прикладных программ Statistica. М.: Медиасфера; 2002.
  25. Фишер Р. А. Статистические методы для исследователей. М.: Госстатиздат, 1958.
  26. Гланц С. Медико-биологическая статистика: Пер. с англ. М.: Практика; 1998.
  27. Ластед Л. Б. Введение в проблему принятия решений в медицине. М.: Мир; 1971.
  28. Гублер Е. В. Вычислительные методы анализа и распознавания патологических процессов. Л.: Медицина; 1983.
  29. Pascual M., Nieto A., Mataran L. et al. IL-6 promoter polymorphisms in rheumatoid arthritis. Genes and Immunity 2000; 1: 338-340.

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