Skip to main content

Advertisement

Log in

Rheumatoid arthritis risk associates with DNA repair gene XRCC1 Arg399Gln polymorphism in Turkish patients

  • Original Article
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Rheumatoid arthritis (RA) is an autoinflammatory disease with a genetic background. The synoviocytes in RA shows cellular transformation with tumor-like features, and RA patients have genomic instability and relaxation of DNA repair mechanisms. The polymorphisms in BER repair pathway genes, XRCC1 and OGG1, may change the response to inflammation via altered DNA repair capacity. In this study, we aimed to investigate the relationship between the risk of RA and XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms in a group of Turkish RA patients. XRCC1 Arg194Trp, Arg399Gln, and OGG1 Ser326Cys polymorphisms were investigated by PCR–RFLP method in 100 RA patients and 158 healthy control subjects. The results were statistically analyzed by calculating the odds ratios (OR) and their 95% confidence intervals (95% CI) using the χ2-tests. RA patients in this study had significantly higher frequencies of XRCC1 Arg399Gln polymorphism in both homozygote (GG) (35%, OR: 7.78 [95% CI: 3.65–16.59], P < 0.001) and heterozygote (AG) forms (41%, OR: 2.17 [95% CI: 1.19–3.96], P < 0.01) and also increased frequency of 399Gln (G) allele (55%, OR:2.99 [95% CI: 1.67–5.37], P < 0.001). We conclude that XRCC1 Arg194Trp, and OGG1 Ser326Cys polymorphisms are not associated with RA; however, Arg399Gln polymorphism is a significant risk factor of RA, and carriers of 399Gln (G) allele have greater risk of RA.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Orozco G, Rueda B, Martin J (2006) Genetic basis of rheumatoid arthritis. Biomed Pharmacother 60:656–662. doi:10.1016/j.biopha.2006.09.003

    Article  PubMed  CAS  Google Scholar 

  2. Hitchon CA, El-Gabalawy HS (2004) Oxidation in rheumatoid arthritis. Arthritis Res Ther 6:265–278. doi:10.1186/ar1447

    Article  PubMed  Google Scholar 

  3. Lee SH, Chang DK, Goel A, Boland CR, Bugbee W, Boyle DL, Firestein GS (2003) Microsatellite instability and suppressed DNA repair enzyme expression in rheumatoid arthritis. J Immunol 170:2214–2220

    PubMed  CAS  Google Scholar 

  4. Raychaudhuri S (2010) Recent advances in the genetics of rheumatoid arthritis. Curr Opin Rheum 22:109–118. doi:10.1097/BOR.0b013e328336474d

    Article  CAS  Google Scholar 

  5. Amouroux R, Campalans A, Epe B, Radicella JP (2010) Oxidative stress triggers the preferential assembly of base excision repair complexes on open chromatin regions. Nucleic Acids Res 38(9):2878–2890. doi:10.1093/nar/gkp1247

    Article  PubMed  CAS  Google Scholar 

  6. Mabley JG, Pacher P, Deb A, Wallace R, Elder RH, Szabo C (2005) Potential role for 8-oxoguanine DNA glycosylase in regulating inflammation. FASEB J 19(2):290–292. doi:10.1096/fj.04-2278fje

    PubMed  CAS  Google Scholar 

  7. Marsin S, Vidal AE, Sossou M, Menissier-de Murcial J, Le Page F, Boiteux S, de Murcial G, Radicella JP (2003) Role of XRCC1 in the coordination and stimulation of oxidative DNA damage repair initiated by the DNA glycosylase hOGG1. J Biol Chem 278:44068–44074

    Google Scholar 

  8. Monaco R, Rosal R, Dolan MA, Pincus MR, Brandt-Rauf PW (2007) Conformational effects of a common codon 399 polymorphism on the BRCT1 domain of the XRCC1 protein. Protein J 26(8):541–546

    Article  PubMed  CAS  Google Scholar 

  9. Clarke A, Vyse TJ (2009) Genetics of rheumatic disease. Arthritis Res Ther 11(5):248. doi:10.1186/ar2781

    Article  PubMed  Google Scholar 

  10. Meira LB, Bugni JM, Green SL, Lee CW, Pang B, Borenshtein D, Rickman BH, Rogers AB, Moreski-Ergul CA, McFaline JL, Schauer DB, Dedon PC, Fox JG, Samson LD (2005) DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice. J Clin Invest 118(7):2516–2525. doi:10.1172/JCI35073

    Google Scholar 

  11. Koyama A, Kubota Y, Shimamura T, Horiuchi S (2006) Possible association of the X-ray cross complementing gene 1 (XRCC1) Arg280His polymorphism as a risk factor for rheumatoid arthritis. Rheumatol Int 26:749–751. doi:10.1007/s00296-005-0066-3

    Article  PubMed  Google Scholar 

  12. Hung RJ, Hall J, Brennan P, Boffetta P (2005) Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review. Am J Epidemiol 162(10):925–942. doi:10.1093/aje/kw/i318

    Article  PubMed  Google Scholar 

  13. Kocabas NA, Karahalil B (2006) XRCC1 Arg399Gln genetic polymorphism in a Turkish population. Int J Toxicol 25:419–422. doi:10.1080/10915810600870567

    Article  PubMed  CAS  Google Scholar 

  14. Kohno T, Shinmura K, Tosaka M, Tani M, Kim SR, Sugimura H, Nohmi T, Kasai H, Yokota J (1998) Genetic polymorphisms and alternative splicing of the hOGG1 gene, that is involved in the repair of 8-hydroxyguanine in damaged DNA. Oncogene 16:3219–3225

    Article  PubMed  CAS  Google Scholar 

  15. Lin YJ, Wan L, Huang CM, Chen SY, Huang YC, Lai CH, Lin WY, Liu HP, Wu YS, Chen CM, Tsai YH, Tsai CH, Sheu CCJ, Tsai FJ (2009) Polymorphisms in the DNA repair gene XRCC1 and associations with systemic lupus erythematosus risk in the Taiwanese Han Chinese population. Lupus 18:1246–1251. doi:10.1177/0961203309345777

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the patients and volunteers, who participated in this study. This study was not financially supported by any governmental or non-governmental funds, and the authors report no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elif Yosunkaya.

Author contributions

Author contributions

Each author in this paper contributed to various aspects of this study: Patient recruitment and clinical data collections by F. Karakurt, E. Cetin, and L. Ozgonenel, DNA isolation and genotyping performed by B. Batar, study designed by I. Onaran, M. Guven and G. Kanigur-Sultuybek, data interpretation and preparation of the manuscript performed by E. Yosunkaya.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yosunkaya, E., Karakurt, F., Cetin, E. et al. Rheumatoid arthritis risk associates with DNA repair gene XRCC1 Arg399Gln polymorphism in Turkish patients. Rheumatol Int 32, 1265–1269 (2012). https://doi.org/10.1007/s00296-010-1725-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-010-1725-6

Keywords

Navigation