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Chemokine receptor 5 Δ32 polymorphism and systemic lupus erythematosus, vasculitis, and primary Sjogren’s syndrome

Meta-analysis of possible associations

Chemokinrezeptor 5-Δ32-Polymorphismus und systemischer Lupus erythematosus, Vaskulitis sowie Sjögren-Syndrom

Eine Metaanalyse möglicher Zusammenhänge

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Abstract

Objective

The aim of this study was to determine whether the functional chemokine receptor 5 delta32 (CCR5-Δ32) polymorphism is associated with susceptibility to systemic lupus erythematosus (SLE), vasculitis, and primary Sjogren’s syndrome (pSS).

Results

A total of 12 studies were analyzed, including 5 on SLE, 5 on vasculitis, and 2 on pSS, encompassing 1881 patients and 2391 controls. Meta-analysis indicated no association between SLE and the CCR5-Δ32 allele (OR 0.842, 95 % CI 0.793–1.804, p = 0.657), and no association between the CCR5-Δ32 allele and SLE in Europeans (OR 0.647, 95 % CI 0.306–1.368, p = 0.255). Meta-analysis of the CCR5-Δ32 allele and the Δ32Δ32 + Δ32 W genotype showed no association with lupus nephritis (LN; OR 1.771, 95 % CI 0.475–6.595, p = 0.395; OR 2.192, 95 % CI 0.182–26.42, p = 0.537, respectively). In addition, meta-analysis revealed no association between the CCR5-Δ32 allele and vasculitis in all study subjects and in Europeans (OR 1.241, 95 % CI 0.951–1.620, p = 0.111; OR 1.359, 95 % CI 0.803–2.303, p = 0.254, respectively). However, the overall OR for the CCR5-Δ32 allele was significantly higher in Kawasaki disease (KD; OR 1.746, 95 % CI 1.003–2.955, p = 0.038) and the meta-analysis of the Δ32Δ32 + Δ32 W genotype showed a trend indicating an association with KD (OR 1.683, 95 % CI 0.921–3.077, p = 0.091). No association was found between the CCR5-Δ32 polymorphism and pSS.

Conclusion

This meta-analysis demonstrates that the CCR5-Δ32 polymorphism is associated with KD, but does not facilitate susceptibility to SLE, LN, or pSS.

Zusammenfassung

Ziel

Mit der Studie sollte ermittelt werden, ob der funktionelle Chemokinrezeptor 5-Δ32(CCR5-Δ32)-Polymorphismus mit einer Suszeptibilität für den systemischen Lupus erythematosus (SLE), eine Vaskulitis oder das primäre Sjögren-Syndrom (pSS) einhergeht.

Ergebnisse

Einbezogen wurden 12 Studien, 5 zu SLE, 5 zu Vaskulitis und 2 zum pSS, mit insgesamt 1881 Patienten und 2391 Kontrollpersonen. Die Metaanalyse ergab keinen Zusammenhang zwischen SLE und dem CCR5-Δ32-Allel (OR 0,842, 95%–KI 0,793–1,804, p=0,657), auch keinen zwischen dem CCR5-Δ32-Allel und SLE bei europäischen Patienten (OR 0,647, 95%-KI 0,306–1,368, p=0,255). Ferner ergab sich keine Assoziation zwischen Lupusnephritis, dem CCR5-Δ32-Allel und Δ32Δ32+Δ32 W-Genotyp (OR 1,771, 95%-KI 0,475–6,595, p=0,395; OR 2,192, 95%–KI 0,182–26,42, p=0,537). Zusätzlich zeigte sich in der Metaanalyse keine Assoziation zwischen dem CCR5-Δ32-Allel und einer Vaskulitis bei allen Studienpatienten und bei europäischen Studienteilnehmern (OR 1,241, 95%-KI 0,951–1,620, p=0,111; OR 1,359, 95%-KI 0,803–2,303, p=0,254). Doch die Gesamt-OR für das CCR5-Δ32-Allel war signifikant höher bei Kawasaki-Syndrom-Patienten (OR 1,746, 95%-KI 1,003–2,955, p=0,038), und der Trend bei der Metaanalyse des Δ32Δ32+Δ32 W-Genotyps wies auf eine KD-Assoziation hin (OR 1,683, 95%-KI 0,921–3,077, p=0,091). Zwischen dem CCR5-Δ32-Polymporphismus und einem pSS zeigte sich keine Assoziation.

Fazit

Diese Metaanalyse weist nach, dass der CCR5-Δ32-Polymorphismus zwar mit dem Kawasaki-Syndrom assoziiert ist, nicht aber die Suszeptibilität für SLE, LN oder pSS erhöht.

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References

  1. Lee YH, Nath SK (2005) Systemic lupus erythematosus susceptibility loci defined by genome scan meta-analysis. Hum Genet 118:434–443

    Article  PubMed  Google Scholar 

  2. Kang SH, Chung BH, Choi SR et al (2011) Comparison of clinical outcomes by different renal replacement therapy in patients with end-stage renal disease secondary to lupus nephritis. Korean J Intern Med 26:60–67

    Article  PubMed Central  PubMed  Google Scholar 

  3. Fox RI (2005) Sjogren’s syndrome. Lancet 366:321–331

    Article  CAS  PubMed  Google Scholar 

  4. Lee YH, Song GG (2012) Associations between eNOS polymorphisms and susceptibility to Behcet’s disease: a meta-analysis. J Eur Acad Dermatol Venereol 26:1266–1271

    Article  CAS  PubMed  Google Scholar 

  5. Szekanecz Z, Kim J, Koch AE (2003) Chemokines and chemokine receptors in rheumatoid arthritis. Semin Immunol 15:15–21

    Article  CAS  PubMed  Google Scholar 

  6. Wu L, LaRosa G, Kassam N et al (1997) Interaction of chemokine receptor CCR5 with its ligands: multiple domains for HIV-1 gp120 binding and a single domain for chemokine binding. J Exp Med 186:1373–1381

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Liu R, Paxton WA, Choe S et al (1996) Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86:367–377

    Article  CAS  PubMed  Google Scholar 

  8. Benkirane M, Jin DY, Chun RF et al (1997) Mechanism of transdominant inhibition of CCR5-mediated HIV-1 infection by ccr5delta32. J Biol Chem 272:30603–30606

    Article  CAS  PubMed  Google Scholar 

  9. Carvalho C, Calvisi SL, Leal B et al (2013) CCR5-Delta32: implications in SLE development. Int J Immunogenet

  10. Schauren JS, Marasca JA, Veit TD et al (2013) CCR5delta32 in systemic lupus erythematosus: implications for disease susceptibility and outcome in a Brazilian population. Lupus 22:802–809

    Article  CAS  PubMed  Google Scholar 

  11. Aguilar F, Nunez-Roldan A, Torres B et al (2003) Chemokine receptor CCR2/CCR5 polymorphism in Spanish patients with systemic lupus erythematosus. J Rheumatol 30:1770–1774

    CAS  PubMed  Google Scholar 

  12. Maier-Moore JS, Canas CA, Tobon G et al (2013) The CCR5 delta 32 polymorphism (rs333) is not associated with Sjogren’s syndrome or Type 1 Diabetes in Colombians. Clin Immunol 148:206–208

    Article  CAS  PubMed  Google Scholar 

  13. Petrek M, Cermakova Z, Hutyrova B et al (2002) CC chemokine receptor 5 and interleukin-1 receptor antagonist gene polymorphisms in patients with primary Sjogren’s syndrome. Clin Exp Rheumatol 20:701–703

    CAS  PubMed  Google Scholar 

  14. Chaudhuri K, Singh Ahluwalia T, Singh S et al (2011) Polymorphism in the promoter of the CCL5 gene (CCL5G-403A) in a cohort of North Indian children with Kawasaki disease. A preliminary study. Clin Exp Rheumatol 29(Suppl 64):S126–S130

    PubMed  Google Scholar 

  15. Carmona FD, Rodriguez-Rodriguez L, Castaneda S et al (2011) Role of the CCR5/Delta32CCR5 polymorphism in biopsy-proven giant cell arteritis. Hum Immunol 72:458–461

    Article  CAS  PubMed  Google Scholar 

  16. Breunis WB, Biezeveld MH, Geissler J et al (2007) Polymorphisms in chemokine receptor genes and susceptibility to Kawasaki disease. Clin Exp Immunol 150:83–90

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Zhou Y, Huang D, Farver C, Hoffman GS (2003) Relative importance of CCR5 and antineutrophil cytoplasmic antibodies in patients with Wegener’s granulomatosis. J Rheumatol 30:1541–1547

    CAS  PubMed  Google Scholar 

  18. Pazzola G, Boiardi L, Casali B et al (2013) CC chemokine receptor 5 polymorphism in Italian patients with giant cell arteritis. Mod Rheumatol 23:851–855

    Article  CAS  PubMed  Google Scholar 

  19. Yang SG, Ye DQ, Li XP et al (2003) The SNPs of chemokine RANTES promoter and the mutation of its’ receptor CCR5 in SLE and controls in Han indigenous in Chinese. Chin J Microbiol Immunol 23:723–727

    CAS  Google Scholar 

  20. Lee YH, Witte T, Momot T et al (2005) The mannose-binding lectin gene polymorphisms and systemic lupus erythematosus: two case-control studies and a meta-analysis. Arthritis Rheum 52:3966–3974

    Article  CAS  PubMed  Google Scholar 

  21. Nath SK, Harley JB, Lee YH (2005) Polymorphisms of complement receptor 1 and interleukin-10 genes and systemic lupus erythematosus: a meta-analysis. Hum Genet 118:225–234

    Article  CAS  PubMed  Google Scholar 

  22. Lee YH, Harley JB, Nath SK (2006) Meta-analysis of TNF-alpha promoter -308 A/G polymorphism and SLE susceptibility. Eur J Hum Genet 14:364–371

    Article  CAS  PubMed  Google Scholar 

  23. Liberati A, Altman DG, Tetzlaff J et al (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151:W65–W94

    Article  PubMed  Google Scholar 

  24. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Davey Smith G, Egger M (1997) Meta-analyses of randomised controlled trials. Lancet 350:1182

    Google Scholar 

  26. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  CAS  PubMed  Google Scholar 

  27. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  28. Mamtani M, Rovin B, Brey R et al (2008) CCL3L1 gene-containing segmental duplications and polymorphisms in CCR5 affect risk of systemic lupus erythaematosus. Ann Rheum Dis 67:1076–1083

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Jhang WK, Kang MJ, Jin HS et al (2009) The CCR5 (-2135C/T) polymorphism may be associated with the development of Kawasaki disease in Korean children. J Clin Immunol 29:22–28

    Article  CAS  PubMed  Google Scholar 

  30. Bidyalaxmi Devi L, Bhatnagar A, Wanchu A, Sharma A (2013) A study on the association of autoantibodies, chemokine, and its receptor with disease activity in systemic lupus erythematosus in North Indian population. Rheumatol Int 33:2819–2826

    Article  Google Scholar 

  31. Atzeni F, Boiardi L, Casali B et al (2012) CC chemokine receptor 5 polymorphism in Italian patients with Behcet’s disease. Rheumatology (Oxford) 51:2141–2145

    Google Scholar 

  32. Yang X, Ahmad T, Gogus F et al (2004) Analysis of the CC chemokine receptor 5 (CCR5) Delta32 polymorphism in Behcet’s disease. Eur J Immunogenet 31:11–14

    Article  CAS  PubMed  Google Scholar 

  33. Jones KL, Maguire JJ, Davenport AP (2011) Chemokine receptor CCR5: from AIDS to atherosclerosis. Br J Pharmacol 162:1453–1469

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Lee YH, Rho YH, Choi SJ et al (2007) PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Rheumatol Int 27:827–833

    Article  CAS  PubMed  Google Scholar 

  35. Newburger JW, Fulton DR (2004) Kawasaki disease. Curr Opin Pediatr 16:508–514

    Article  PubMed  Google Scholar 

  36. Turner JE, Paust HJ, Steinmetz OM et al (2008) CCR5 deficiency aggravates crescentic glomerulonephritis in mice. J Immunol 181:6546–6556

    Article  CAS  PubMed  Google Scholar 

  37. Paxton WA, Kang S (1998) Chemokine receptor allelic polymorphisms: relationships to HIV resistance and disease progression. Semin Immunol 10:187–194

    Article  CAS  PubMed  Google Scholar 

  38. Prahalad S (2006) Negative association between the chemokine receptor CCR5-Delta32 polymorphism and rheumatoid arthritis: a meta-analysis. Genes Immun 7:264–268

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Compliance with ethical guidelines

Conflict of interest. Y.H. Lee, J.-H. Kim, and G.G. Song state that there are no conflicts of interest. The accompanying manuscript does not include studies on humans or animals.

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Korea University College of Medicine, 126-1, Anam-dong 5-ga, Seongbuk-gu , 136-705, Seoul, Korea

    Y.H. Lee MD, PhD, J.-H. Kim & G.G. Song

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  1. Y.H. Lee MD, PhD
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  3. G.G. Song
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Correspondence to Y.H. Lee MD, PhD.

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Lee, Y., Kim, JH. & Song, G. Chemokine receptor 5 Δ32 polymorphism and systemic lupus erythematosus, vasculitis, and primary Sjogren’s syndrome. Z. Rheumatol. 73, 848–855 (2014). https://doi.org/10.1007/s00393-014-1356-5

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