Skip to main content

Advertisement

SpringerLink
Log in

The CC chemokine ligand 2 (CCL2) polymorphism −2518A/G is associated with gout in the Chinese Han male population

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

Abstract

Gout is usually characterized by uric acid-induced recurrent attacks of acute inflammatory arthritis. CC chemokine ligand 2 (CCL2), a chemokine involved in the recruitment and migration of monocytes/macrophages, has previously been shown to be increased in the plasma of gout patients. In this study, we examined whether the CCL2 −2518A/G (rs1024611) single nucleotide polymorphism (SNP) affects susceptibility to gout in a Chinese Han male population. Genomic DNA from gout patients (n = 1,109) and ethnically matched gout-free controls (n = 1,034) was genotyped for the CCL2 −2518A/G SNP using polymerase chain reaction–restriction fragment length polymorphism. The Chi-square test was performed to investigate the association of genotypic and allelic frequencies between cases and controls, and the −2518G allele was shown to be associated with a significantly increased risk of gout development [P = 0.007, odds ratio 1.182, 95 % confidence interval 1.047–1.335]. The GG genotypic distribution was also significantly different between cases and controls (adjusted P = 0.021). However, genotypic distributions and allelic frequencies did not indicate significant associations (P = 0.150 and P = 0.050, respectively) between tophi and non-tophi patients. Our findings support a key role for the CCL2 SNP −2518A/G in association with gout susceptibility in the Chinese Han male population. However, additional studies in other populations should be carried out to confirm this finding.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Choi HK, Mount DB, Reginato AM (2005) Pathogenesis of gout. Ann Intern Med 143:499–516

    Article  CAS  PubMed  Google Scholar 

  2. Matsukawa A, Miyazaki S, Maeda T, Tanase S, Feng L et al (1998) Production and regulation of monocyte chemoattractant protein-1 in lipopolysaccharide-or monosodium urate crystal-induced arthritis in rabbits: roles of tumor necrosis factor alpha, interleukin-1, and interleukin-8. Lab Invest 78:973–985

    CAS  PubMed  Google Scholar 

  3. Zheng W, Li R, Pan H, He D, Xu R et al (2009) Role of osteopontin in induction of monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β through the NF-κB and MAPK pathways in rheumatoid arthritis. Arthritis Rheum 60:1957–1965

    Article  CAS  PubMed  Google Scholar 

  4. Harigai M, Hara M, Yoshimura T, Leonard EJ, Inoue K et al (1993) Monocyte chemoattractant protein-1 (CCL2) in inflammatory joint diseases and its involvement in the cytokine network of rheumatoid synovium. Clin Immunol Immunopathol 69:83–91

    Article  CAS  PubMed  Google Scholar 

  5. Grainger R, McLaughlin RJ, Harrison AA, Harper JL (2013) Hyperuricaemia elevates circulating CCL2 levels and primes monocyte trafficking in subjects with inter-critical gout. Rheumatology 52:1018–1021

    Article  CAS  PubMed  Google Scholar 

  6. Fenoglio et al. (2004) CCL2 in Alzheimer’s disease patients: a −2518G polymorphism and serum levels by neurobiol aging 25(9):1169–1173

  7. Karrer S, Bosserhoff AK, Weiderer P, Distler O, Landthaler M et al (2005) The −2518 promotor polymorphism in the CCL2 gene is associated with systemic sclerosis. J Invest Dermatol 124:92–98

    Article  CAS  PubMed  Google Scholar 

  8. Gao Q, Du Q, Zhang H, Guo C, Lu S et al (2014) Monocyte chemotactic protein-1 −2518 gene polymorphism and susceptibility to spinal tuberculosis. Arch Med Res 45:183–187

    Article  CAS  PubMed  Google Scholar 

  9. Song GG, Lee YH (2013) The CTLA-4 and CCL2 polymorphisms and susceptibility to systemic sclerosis: a meta-analysis. Immunol Invest 42:481–492

    Article  CAS  PubMed  Google Scholar 

  10. Lin HL, Ueng KC, Hsieh YS, Chiang WL, Yang SF et al (2012) Impact of CCL2 and CCR-2 gene polymorphisms on coronary artery disease susceptibility. Mol Biol Rep 39:9023–9030

    Article  CAS  PubMed  Google Scholar 

  11. Brown KS, Nackos E, Morthala S, Jensen LE, Whitehead AS et al (2007) Monocyte chemoattractant protein-1: plasma concentrations and A (−2518) G promoter polymorphism of its gene in systemic lupus erythematosus. J Rheumatol 34:740–746

    CAS  PubMed  Google Scholar 

  12. Miao Z, Li C, Chen Y, Zhao S, Wang Y et al (2008) Dietary and lifestyle changes associated with high prevalence of hyperuricemia and gout in the Shandong coastal cities of Eastern China. J Rheumatol 35:1859–1864

    PubMed  Google Scholar 

  13. Luk AJ, Simkin PA (2005) Epidemiology of hyperuricemia and gout. Am J Manag Care 11:S435–S442

    PubMed  Google Scholar 

  14. Sundy JS, Hershfield MS (2007) Uricase and other novel agents for the management of patients with treatment-failure gout. Curr Rheumatol Rep 9:258–264

    Article  CAS  PubMed  Google Scholar 

  15. Wallace SL, Robinson H, Masi AT, Decker JL, McCarty DJ et al (1977) Preliminary criteria for the classification of the acute arthritis of primary gout. Arthritis Rheum 20:895–900

    Article  CAS  PubMed  Google Scholar 

  16. Mikuls TR, Farrar JT, Bilker WB, Fernandes S, Schumacher HR Jr et al (2005) Gout epidemiology: results from the UK general practice research database, 1990–1999. Ann Rheum Dis 64:267–272

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Pierer M, Rethage J, Seibl R, Lauener R, Brentano F et al (2004) Chemokine secretion of rheumatoid arthritis synovial fibroblasts stimulated by Toll-like receptor 2 ligands. J Immunol 172:1256–1265

    Article  CAS  PubMed  Google Scholar 

  18. Yao TC, Kuo ML, See LC, Ou LS, Lee WI et al (2006) RANTES and monocyte chemoattractant protein 1 as sensitive markers of disease activity in patients with juvenile rheumatoid arthritis: a six-year longitudinal study. Arthritis Rheum 54:258–2593

    Article  Google Scholar 

  19. Ogura N, Satoh K, Akutsu M, Tobe M, Kuyama K et al (2010) CCL2 production in temporomandibular joint inflammation. J Dent Res 89:1117–1122

    Article  CAS  PubMed  Google Scholar 

  20. Ahmed S, Pakozdi A, Koch AE (2006) Regulation of interleukin-1beta-induced chemokine production and matrix metalloproteinase 2 activation by epigallocatechin-3-gallate in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 54:2393–2401

    Article  CAS  PubMed  Google Scholar 

  21. Liu S, Yin C, Chu N, Han L, Li C (2013) IL-8-251T/A and IL-12B 1188A/C polymorphisms are associated with gout in a Chinese male population. Scand J Rheumatol 42:150–158

    Article  CAS  PubMed  Google Scholar 

  22. Liu S, Wang H, Li C (2013) Relationship between -238A/G and -308A/G polymorphisms in the promoter region of TNF-α and susceptibility to gout in the Chinese Han male population. Cent Eur J Immunol 38:449–453

    Article  Google Scholar 

  23. Chang SJ, Chen CJ, Tsai FC, Lai HM, Tsai PC et al (2008) Associations between gout tophus and polymorphisms 869T/C and -509C/T in transforming growth factor beta1 gene. Rheumatology 47:617–621

    Article  CAS  PubMed  Google Scholar 

  24. Chang SJ, Tsai PC, Chen CJ, Lai HM, Ko YC (2007) The polymorphism −863C/A in tumour necrosis factor-alpha gene contributes an independent association to gout. Rheumatology 46:1662–1666

    Article  CAS  PubMed  Google Scholar 

  25. Rovin BH, Lu L, Saxena R (1999) A novel polymorphism in the CCL2 gene regulatory region that influences CCL2 expression. Biochem Biophys Res Commun 259:344–348

    Article  CAS  PubMed  Google Scholar 

  26. Pham MH, Bonello GB, Castiblanco J et al (2012) The rs1024611 regulatory region polymorphism is associated with CCL2 allelic expression imbalance. PLoS ONE 7(11):e49498

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank all of the probands for their participation. This work was supported by the National Science Foundation of China (81070686 and 31371272).

Confict of interest

None.

Author information

Authors and Affiliations

  1. Shandong Provincial Key Laboratory of Metabolic Disease, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, 266003, China

    Ruixia Sun, Keke Zhang, Xiaokun Zhang, Lingling Cui, Can Wang, Shiguo Liu & Changgui Li

  2. Institute of Clinical Research, The Affiliated Hospital of Medical College, Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China

    Ruixia Sun, Keke Zhang, Xiaokun Zhang, Lingling Cui, Can Wang, Shiguo Liu & Changgui Li

  3. Genetic Laboratory, The Affiliated Hospital of Medical College, Qingdao University, Qingdao, 266003, China

    Qingsheng Mi & Shiguo Liu

Authors
  1. Ruixia Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Keke Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaokun Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lingling Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Can Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Qingsheng Mi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shiguo Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Changgui Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Shiguo Liu or Changgui Li.

Additional information

Ruixia Sun and Keke Zhang contributed equally to the work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, R., Zhang, K., Zhang, X. et al. The CC chemokine ligand 2 (CCL2) polymorphism −2518A/G is associated with gout in the Chinese Han male population. Rheumatol Int 35, 479–484 (2015). https://doi.org/10.1007/s00296-014-3102-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-014-3102-3

Keywords

Search

Navigation