Skip to main content

Advertisement

Log in

Lack of association of TLR4 gene Asp299Gly and Thr399Ile polymorphisms with rheumatoid arthritis in Chinese Han population of Yunnan Province

  • Short Communication
  • Published:
Rheumatology International Aims and scope Submit manuscript

Abstract

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of synovium and subsequent joint destruction. Recently, genetic polymorphisms within the toll-like receptor 4 (TLR4) genes have been reported to be associated with RA. To analyze the association between the genetic polymorphisms within TLR4 gene and the susceptibility to RA in Chinese people, two functional variants, Asp299Gly and Thr399Ile, in the TLR4 gene were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and direct sequencing techniques from 213 RA patients and 247 ethnically matched controls. None polymorphisms of Asp299Gly and Thr399Ile were detected in all RA cases and controls, which indicates that there is no relevance between these two SNPs and RA in the Chinese Han population. Further studies with extended single nucleotide polymorphisms (SNP) should be performed.

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.

References

  1. Lawrence JS, Heberden Oration (1970) 1969: rheumatoid arthritis: nature or nurture? Ann Rheum Dis 29:357–379

    Article  CAS  PubMed  Google Scholar 

  2. Orozco G, Rueda B, Martin J (2006) Genetic basis of rheumatoid arthritis. Biomed Pharmacother 60:656–662

    Article  CAS  PubMed  Google Scholar 

  3. Wordsworth BP, Lanchbury JS, Sakkas LI, Welsh KI, Panayi GS, Bell JI (1989) HLA-DR4 subtype frequencies in rheumatoid arthritis indicate that DRB1 is the major susceptibility locus within the HLA classII region. Proc Natl Acad Sci 86:10049–10053

    Article  CAS  PubMed  Google Scholar 

  4. Deighton CM, Walker DJ, Griffiths ID, Roberts DF (1989) The contribution of HLA to rheumatoid arthritis. Clin Genet 36:178–182

    Article  CAS  PubMed  Google Scholar 

  5. Radstake TR, Franke B, Hanssen S, Netea MG, Welsing P, Barrera P et al (2004) The toll-like receptor 4 Asp299Gly functional variant is associated with decreased rheumatoid arthritis disease susceptibility but does not influence disease severity and/or outcome. Arthritis Rheum 50:999–1001

    Article  CAS  PubMed  Google Scholar 

  6. Kilding R, Akil M, Till S, Amos R, Winfield J, Iles MM et al (2003) A biologically important single nucleotide polymorphism within the toll-like receptor-4 gene is not associated with rheumatoid arthritis. Clin Exp Rheumatol 21:340–342

    CAS  PubMed  Google Scholar 

  7. Sanchez E, Orozco G, Lopez-Nevot MA, Jimenez-Alonso J, Martin J (2004) Polymorphisms of toll-like receptor 2 and 4 genes in rheumatoid arthritis and systemic lupus erythematosus. Tissue Antigens 63:54–57

    Article  CAS  PubMed  Google Scholar 

  8. Sheedy FJ, Marinou I, O’Neill LAJ, Wilson AG (2008) The Mal/TIRAP S180L and TLR4 G299D polymorphisms are not associated with susceptibility to or severity of rheumatoid arthritis. Ann Rheum Dis 67:1328–1331

    Article  CAS  PubMed  Google Scholar 

  9. Medzhitov R, Preston-Hurlburt P Jr, Janeway CA (1997) A human homologous of the drosophila toll protein signals activation of adaptive immunity. Nature 388:394–397

    Article  CAS  PubMed  Google Scholar 

  10. Akira S, Takeda K, Kaisho T (2001) Toll-like receptors: critical proteins linking innate and acquired immunity. Nat Immunol 2:675–680

    Article  CAS  PubMed  Google Scholar 

  11. Poltorak A, He X, Smirnova I et al (1998) Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 282:2085–2088

    Article  CAS  PubMed  Google Scholar 

  12. Hoshino K, Takeuchi O, Kawai T et al (1999) Toll-like receptor 4 (TLR4)–deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product. J Immunol 162:3749–3752

    CAS  PubMed  Google Scholar 

  13. Ohashi K, Burkart V, Flohe S, Kolb H (2000) Cutting edge: heat shock protein 60 is a putative endogenous ligand of the toll-like receptor-4 complex. J Immunol 164:558–561

    CAS  PubMed  Google Scholar 

  14. Termeer C, Benedix F, Sleeman J, Fieber C, Voith U, Ahrens T et al (2002) Oligosaccharides of hyaluronan activate dendritic cells via toll-like receptor4. J Exp Med 195:99–111

    Article  CAS  PubMed  Google Scholar 

  15. Okamura Y, Watari M, Jerud ES, Young DW, Ishizaka ST, Rose J et al (2001) The extra domain A of fibronectin activates toll-like receptor 4. J Biol Chem 276:10229–10233

    Article  CAS  PubMed  Google Scholar 

  16. Arbour NC, Lorenz E, Schutte BC, Zabner J, Kline JN, Jones M et al (2000) TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 25:187–191

    Article  CAS  PubMed  Google Scholar 

  17. Erridge C, Stewart J, Poxton IR (2003) Monocytes heterozygous for the Asp299Gly and Thr399Ile mutations in the toll-like receptor 4 gene show no deficit in lipopolysaccharide signalling. J Exp Med 197:1787–1791

    Article  CAS  PubMed  Google Scholar 

  18. Hang JQ, Zhou W, Zhang HX et al (2004) TLR4 Asp299Gly and Thr399Ile polymorphisms are very rare in the Chinese population. J Endotoxin Res 10:238–240

    Article  CAS  PubMed  Google Scholar 

  19. Duan ZX, Zhu PF, Dong H et al (2007) Functional significance of the TLR4/11367 polymorphism identified in Chinese Han population. Shock 28:160–164

    Article  CAS  PubMed  Google Scholar 

  20. Guo QS, Xia B, Jiang Y et al (2005) Polymorphisms of CD14 gene and TLR4 gene are not associated with ulcerative colitis in Chinese patients. Postgrad Med J 81:526–529

    Article  CAS  PubMed  Google Scholar 

  21. Cheng PL, Eng HL, Chou MH, You HL, Lin TM (2007) Genetic polymorphisms of viral infection associated Toll-like receptors in Chinese population. Transl Res 150:311–318

    Article  CAS  PubMed  Google Scholar 

  22. Lin YC, Chang YM, Yu JM, Yen JH, Chang JG, Hu CJ (2005) Toll-like receptor 4 gene C119A but no Asp299Gly polymorphism is associated with ischemic stroke among ethnic Chinese in Taiwan. Atherosclerosis 180:305–309

    Article  CAS  PubMed  Google Scholar 

  23. Okayama N, Fujimura K, Suehiro Y et al (2002) Simple genotype analysis of the Asp299Gly polymorphism of the toll like receptor 4 gene that is associated with lipopolysaccharide hyporesponsiveness. J Clin Lab Anal 16:56–58

    Article  CAS  PubMed  Google Scholar 

  24. Nakada TA, Hirasawa H, Oda S et al (2005) Influence of toll-like receptor 4, CD14, tumor necrosis factor, and interleukine-10 gene polymorphisms on clinical outcome in Japanese critically ill patients. J Surg Res 129:322–328

    Article  CAS  PubMed  Google Scholar 

  25. Kim YS, Hwang YJ, Kim SY, Yang SM, Lee KY, Park IB (2008) Rarity of TLR4 Asp299Gly and Thr399Ile polymorphisms in the Korean population. Yonsei Med J 49:58–62

    Article  CAS  PubMed  Google Scholar 

  26. Mockenhaupt FP, Cramer JP, Hamann L et al (2006) Toll-like receptor (TLR) polymorphisms in African children: common TLR-4 variants predispose to severe malaria. Proc Natl Acad Sci 103:177–182

    Article  CAS  PubMed  Google Scholar 

  27. Arbour NC, Lorenz E, Schutte BC et al (2000) TLR4 mutations are associated with endotoxin hyporesponsiveness in humans. Nat Genet 25:187–191

    Article  CAS  PubMed  Google Scholar 

  28. Adam R, Sturrock RD, Gracie JA (2006) TLR4 mutations (Asp299Gly and Thr399Ile) are not associated with ankylosing spondylitis. Ann Rheum Dis 65:1099–1101

    Article  CAS  PubMed  Google Scholar 

  29. Agnese DM, Calvano JE, Hahm SJ et al (2002) Human toll-like receptor 4 mutations but not CD14 polymorphisms are associated with an increased risk of gramnegative infections. J Infect Dis 186:1522–1525

    Article  CAS  PubMed  Google Scholar 

  30. Carvalhoa A, Marquesb A, Maciela P, Rodrigues F (2007) Study of disease-relevant polymorphisms in the TLR4 and TLR9 genes: a novel method applied to the analysis of the Portuguese population. Mol Cell Probes 21:316–320

    Article  CAS  Google Scholar 

  31. Hawn TR, Verbon A, Janer M, Zhao LP, Beutler B, Aderem A (2005) Toll-like receptor 4 polymorphisms are associated with resistance to Legionnaires’ disease. Proc Natl Acad Sci 102:487–2489

    Google Scholar 

  32. Paulus SC, Hirschfeld AF, Victor RE, Brunstein J, Thomas E, Turvey SE (2007) Common human toll-like receptor 4 polymorphisms—role in susceptibility to respiratory syncytial virus infection and functional immunological relevance. Clin Immunol 123:252–257

    Article  CAS  PubMed  Google Scholar 

  33. Rezazadeh M, Hajilooi M, Rafiei A et al (2006) TLR4 polymorphism in Iranian patients with brucellosis. J Infect 53:206–210

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by The National Nature Science Foundation of China (30660175), Yunnan Province Young Scientist Project (2009CI044), National Undergraduate Students Research Training Found from Ministry of Education of China(81067301), National Found for Fostering Talents of Basic Science (J0730652) and Research Training Found from Yunnan University Experiment Teaching Center of Life Sciences.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Bingrong Zheng or Chunjie Xiao.

Additional information

Bingrong Zheng and Qin Li are contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zheng, B., Li, Q., Wei, C. et al. Lack of association of TLR4 gene Asp299Gly and Thr399Ile polymorphisms with rheumatoid arthritis in Chinese Han population of Yunnan Province. Rheumatol Int 30, 1249–1252 (2010). https://doi.org/10.1007/s00296-010-1400-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-010-1400-y

Keywords

Navigation