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The functional variants of endothelial nitric oxide synthase gene associated with rheumatoid arthritis in Turkish adults

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Abstract

This study aimed to investigate whether functional variants of endothelial nitric oxide synthase (eNOS) gene play any role in rheumatoid arthritis (RA) ethiopathogenesis and treatment in the Turkish population. Because, eNOS variants are responsible for alteration of the NO level in plasma, by reducing/increasing the endothelial NO synthesis. In the study, two eNOS gene variants (G894T and intron 4 VNTR A/B) were examined at extracted DNAs from 65 peripheral blood cell of RA patients. For the control, blood samples obtained from 70 healthy persons were studied. Genotyping of molecular variants was performed by PCR-RFLP and/or PCR technique. The data obtained was compared in itself and response to therapy. We found that “TT genotypic frequency” for the G894T variant was significantly associated with RA with an overall risk of 8.3-fold (p 0.029). No association was identified between intron 4 VNTR A/B variant and RA. At the 6 months, the mean visual analog scale (VAS), health assessment questionnaire (HAQ), and disease activity score for 28 joints (DAS 28) improvement was not significant among groups. Improvement in DAS was significantly better in anti-TNF treatment than disease-modifying antirheumatic drugs (DMARD) treatment treated subgroup. We report for the first time that variants in the eNOS “TT” genotype might be contributed to the increased risk of RA in the Turkish population. These results imply that functional variants of eNOS gene might have an effect on RA patients and response to anti-TNF treatment. In addition, the results suggest that eNOS variants might be associated and affect host susceptibility and/or response to treatment in Turkish RA patients.

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References

  1. Kochi Y, Suzuki A, Yamada R, Yamamoto K (2009) Genetics of rheumatoid arthritis: underlying evidence of ethnic differences. J Autoimmun 32:158–162

    Article  CAS  PubMed  Google Scholar 

  2. Canas CA, Tobon CJ, Bonilla-Abadia F (2014) The importance of evolution in the development and course of rheumatoid arthritis. Med Hypothes 82:784–791

    Article  CAS  Google Scholar 

  3. Pratt AG, Isaacs JD, Mattey DL (2009) Current concepts in the pathogenesis of early rheumatoid arthritis. Best Prac Res. Clin Rheumatol 23:37–48

    CAS  Google Scholar 

  4. Coenen MJ, Gregersen PK (2009) Rheumatoid arthritis: a wiew of the current genetic landscape. Genes Immun 10:101–111

    Article  CAS  PubMed  Google Scholar 

  5. Ueki Y, Miyake S, Tominaga Y, Eguchi K (1996) Increased nitric oxide levels in patients with rheumatoid arthritis. J Rheumatol 23:230–236

    CAS  PubMed  Google Scholar 

  6. Bunjevacki V, Maksimovic N, Jekic B, Milic V, Lukovic L, Novak et al (2016) Polymorphisms of the eNOS gene are associated with disease activity in rheumatoid arthritis. Rheumatol Int 36:597–602

    Article  CAS  PubMed  Google Scholar 

  7. Ding H, Hong C, Wang Y, Liu J, Zhang N, Shen C et al (2014) Calreticulin promotes angiogenesis via activating nitric oxide signalling pathway in rheumatoid arthritis. Clin Exp Immunol 178:236–244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Tsuysui M, Tanimoto A, Tamura M, Mukae H, Yanagihara N et al (2015) Significance of nitric oxide synthesases: lessons from triple nitric oxide synthases null mice. J Pharmacol Science 127:42–52

    Article  Google Scholar 

  9. Dong X, Li D, Liu H, Zhao Y (2014) SOD3 and eNOS genotypes are associated with SOD activity and NOx. Exp Therapeutic Med 8:328–334

    CAS  Google Scholar 

  10. Tsukada T, Yokoyama K, Arai T, Takemoto F, Hara S, Yamada A et al (1999) Evidence of association of the ecNOS gene polymorphism with plasma NO metabolite levels in humans. Biochem Biophysic Res Commin 245:190–193

    Article  Google Scholar 

  11. AlFadhli S (2013) Influence of endothelial nitric oxide synthase gene intron-4 27 bp repeat polymorphism on its expression in autoimmune diseases. Dis Marker 34:349–356

    Article  CAS  Google Scholar 

  12. Kucukdeveci AA, Sahin H, Ataman S, Griffiths B, Tennant A (2004) Issues in cross cultural validity: example from the adaptation, reliability and validity testing of a Turkish version of the Stanford Health Assessement questionnaire. Artritis Care Res 51:14–19

    Article  Google Scholar 

  13. Bruce B, Fries JF (2003) The Stanford Health Assessment Questionnaire: a review of its history, issuses, progress, and documentation. J Rheumatol 30:167–178

    PubMed  Google Scholar 

  14. Miller SA, Dykes DD, Polesky HF (1988) A simple salting out procedure for extracting DNA from nucleated cells. Nucleic Acids Res 16:1215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Erciyas K, Pehlivan S, Sever T, Igci M, Pehlivan M, Arslan A, Orbak R (2010) Endothelial nitric oxide synthase gene polymorphisms associated with periodontal diseases in Turkish adults. Af. J Biotechnol 9:3042–3047

    CAS  Google Scholar 

  16. Yarwood A, Huizinga TWJ, Worthington J (2014) The genetics of rheumatoid arthritis: risk and protection in different stages of the evolution of RA. Rheumatology (Oxford) 55:199–209

    Article  Google Scholar 

  17. Ling S, Lai A, Borschukova O, Pumpens P, Holoshitz J (2006) Activation of nitric oxide signaling by the rheumatoid arthritis shared epitope. Arthritis Rheum 54:3423–3432

    Article  CAS  PubMed  Google Scholar 

  18. Brenol CV, Chies JA, Brenol JC, Monticielo OA, Franciscatto P, Birriel F et al (2009) Endothelial nitric oxide synthase T-786C polymorphism in rheumatoid arthritis: association with extraarticular manifestations. Clin Rheumatol 28:201–215

    Article  PubMed  Google Scholar 

  19. An JD, Li XY, Yu JB, Zhao Y, Jin ZS (2012) Association between the eNOS gene polymorphisms and rheumatoid arthritis risk in the northern Chinese population. Chin Med J 125:1496–1499

    PubMed  Google Scholar 

  20. Ali AM, Habeeb RA, El-Azizi NO, Khattab DA, Abo-Shady RA, Elkabarity RH (2014) Higher nitric oxide levels are associated with disease activity in Egyptian rheumatoid arthritis patients. Rev Bras Rheumatol 54:446–451

    Article  Google Scholar 

  21. Veselinovic M, Barudzic N, Vuletic M, Zivkovic V, Tomic-Lucic A, Dijuric D, Jakovljevic V (2014) Oxidative stress in rheumatoid arthritis patients: relationship to disease activity. Moll. Cell Biochem 391:225–232

    Article  CAS  Google Scholar 

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Acknowledgments

We thank the patients of the Şahinbey Research and Application Hospital of Gaziantep University for their participation in this study. This study was presented with a poster presentation at the Human Genetics Conference (Gothenburg, Sweden, June 2010).

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Authors and Affiliations

  1. Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey

    S. Pehlivan

  2. Department of Physical Medicine and Rehabilitation, Faculty of Medicine, Gaziantep University, Üniversite Bulvarı, Şehitkamil, 27310, Gaziantep, Turkey

    A. Aydeniz, O. Altindag & S. Gursoy

  3. Department of Medical Biology and Genetics, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey

    T. Sever & S. Oguzkan-Balci

  4. Department of Hematology, Faculty of Medicine, Gaziantep University, Gaziantep, Turkey

    M. Pehlivan

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  1. S. Pehlivan
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  2. A. Aydeniz
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Correspondence to A. Aydeniz.

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Pehlivan, S., Aydeniz, A., Sever, T. et al. The functional variants of endothelial nitric oxide synthase gene associated with rheumatoid arthritis in Turkish adults. Clin Rheumatol 36, 537–540 (2017). https://doi.org/10.1007/s10067-016-3416-5

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  • DOI: https://doi.org/10.1007/s10067-016-3416-5

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