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Endothelial nitric oxide synthase T-786C polymorphism in rheumatoid arthritis: association with extraarticular manifestations

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Abstract

Several genetic factors were implicated in the pathogenesis of rheumatoid arthritis (RA). A case–control study was carried out to verify the associations of T-786C polymorphism in the promoter region of the endothelial nitric oxide synthase (eNOS) gene with RA. One hundred and five consecutive RA patients and 100 healthy controls were genotyped. The distribution of the T-786C genotype and alleles did not differ significantly between RA patients and controls. Nevertheless, the frequency of extraarticular manifestations was significantly greater among the carriers of the C/C genotype than among carriers of the T/C and T/T genotypes (P = 0.022). The C/C genotype was significantly associated with extraarticular manifestations compared with the T/T and T/C genotypes taken together (OR = 4.9, 95% CI = 1.3–18.9). The C allele was significantly associated with extraarticular manifestations of RA (P corr = 0.032). The results suggested the existence of an association between the T-786C polymorphism of the eNOS gene and extraarticular manifestations of RA.

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References

  1. Barton A, Ollier W (2002) Genetic approaches to the investigation of rheumatoid arthritis. Curr Opin Rheumatol 14:260–269

    Article  PubMed  CAS  Google Scholar 

  2. Wordsworth P, Bell J (1991) Polygenic susceptibility in rheumatoid arthritis. Ann Rheum Dis 50:343–346

    Article  PubMed  CAS  Google Scholar 

  3. Clancy RM, Amin AR, Abramson SB (1998) The role of nitric oxide in inflammation and immunity. Arthritis Rheum 41:1141–1151

    Article  PubMed  CAS  Google Scholar 

  4. Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, Tsui LC, Schappert KT (1993) Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem 268:17478–17488

    PubMed  CAS  Google Scholar 

  5. Casas JP, Bautista LE, Humphries SE, Hingorani AD (2004) Endothelial nitric oxide synthase genotype and ischemic heart disease: meta-analysis of 26 studies involving 23028 subjects. Circulation 109:1359–1365

    Article  PubMed  CAS  Google Scholar 

  6. Rossi GP, Maiolino G (2004) Do meta-analyses of association studies of endothelial nitric oxide synthase variants and ischemic heart disease provide conclusive answers? Circulation 110:e305–e306 (author reply e305–e306)

    Article  PubMed  Google Scholar 

  7. Gonzalez-Gay MA, Llorca J, Sanchez E, Lopez-Nevot MA, Amoli MM, Garcia-Porrua C, Ollier WE, Martin J (2004) Inducible but not endothelial nitric oxide synthase polymorphism is associated with susceptibility to rheumatoid arthritis in northwest Spain. Rheumatology (Oxford) 43:1182–1185

    Article  CAS  Google Scholar 

  8. Salvarani C, Casali B, Nicoli D, Farnetti E, Macchioni P, Catanoso MG, Chen Q, Bajocchi G, Boiardi L (2003) Endothelial nitric oxide synthase gene polymorphisms in giant cell arteritis. Arthritis Rheum 48:3219–3223

    Article  PubMed  CAS  Google Scholar 

  9. Kim JU, Chang HK, Lee SS, Kim JW, Kim KT, Lee SW, Chung WT (2003) Endothelial nitric oxide synthase gene polymorphisms in Behcet’s disease and rheumatic diseases with vasculitis. Ann Rheum Dis 62:1083–1087

    Article  PubMed  CAS  Google Scholar 

  10. Fatini C, Gensini F, Sticchi E, Battaglini B, Angotti C, Conforti ML, Generini S, Pignone A, Abbate R, Matucci-Cerinic M (2002) High prevalence of polymorphisms of angiotensin-converting enzyme (I/D) and endothelial nitric oxide synthase (Glu298Asp) in patients with systemic sclerosis. Am J Med 112:540–544

    Article  PubMed  CAS  Google Scholar 

  11. Serrano NC, Paez C, Correa PA, Anaya JM (2004) Endothelial nitric oxide synthase gene polymorphism is associated with systemic lupus erythematosus. J Rheumatol 31:2163–2168

    PubMed  CAS  Google Scholar 

  12. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324

    Article  PubMed  CAS  Google Scholar 

  13. Lahiri DK, Nurnberger JI Jr (1991) A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 19:5444

    Article  PubMed  CAS  Google Scholar 

  14. Ordonez AJ, Carreira JM, Franco AG, Sanchez LM, Alvarez MV, Garcia EC (2000) Two expressive polymorphisms on the endothelial nitric oxide synthase gene (intron4, 27 bp repeat and -786 T/C) and the venous thromboembolism. Thromb Res 99:563–566

    Article  PubMed  CAS  Google Scholar 

  15. Melchers I, Blaschke S, Hecker M, Cattaruzza M (2006) The -786C/T single-nucleotide polymorphism in the promoter of the gene for endothelial nitric oxide synthase: insensitivity to physiologic stimuli as a risk factor for rheumatoid arthritis. Arthritis Rheum 54:3144–3151

    Article  PubMed  CAS  Google Scholar 

  16. Tanus-Santos JE, Desai M, Flockhart DA (2001) Effects of ethnicity on the distribution of clinically relevant endothelial nitric oxide variants. Pharmacogenetics 11:719–725

    Article  PubMed  CAS  Google Scholar 

  17. Risch NJ (2000) Searching for genetic determinants in the new millennium. Nature 405:847–856

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  19. Abramson SB, Amin AR, Clancy RM, Attur M (2001) The role of nitric oxide in tissue destruction. Best Pract Res Clin Rheumatol 15:831–845

    Article  PubMed  CAS  Google Scholar 

  20. Elewaut D, De Keyser F, De Wever N, Baeten D, Van Damme N, Verbruggen G, Cuvelier C, Veys EM (1998) A comparative phenotypical analysis of rheumatoid nodules and rheumatoid synovium with special reference to adhesion molecules and activation markers. Ann Rheum Dis 57:480–486

    Article  PubMed  CAS  Google Scholar 

  21. Markenson JA (1991) Worldwide trends in the socioeconomic impact and long-term prognosis of rheumatoid arthritis. Semin Arthritis Rheum 21:4–12

    Article  PubMed  CAS  Google Scholar 

  22. Gonzalez-Gay MA, Gonzalez-Juanatey C, Ollier WE (2004) Endothelial dysfunction in rheumatoid arthritis: influence of HLA-DRB1 alleles. Autoimmun Rev 3:301–304

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to acknowledge Marcele Rizzatti and Rafael Pereira for their valuable support. We also thank Charles Kohem, Rafael Chakr, and Tamara Mucenic.

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Correspondence to Ricardo Machado Xavier.

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Brenol, C.V., Chies, J.A.B., Brenol, J.C.T. et al. Endothelial nitric oxide synthase T-786C polymorphism in rheumatoid arthritis: association with extraarticular manifestations. Clin Rheumatol 28, 201–205 (2009). https://doi.org/10.1007/s10067-008-1018-6

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  • DOI: https://doi.org/10.1007/s10067-008-1018-6

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