Skip to main content

Advertisement

Log in

Meta-analysis of associations between functional HLA-G polymorphisms and susceptibility to systemic lupus erythematosus and rheumatoid arthritis

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

Abstract

The aim of this study was to determine whether the functional HLA-G 14 bp insertion (I)/deletion (D) and +3142 G/C polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). A meta-analysis was conducted on the associations between the HLA-G 14 bp I/D, and +3142 G/C polymorphisms and SLE or RA using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) additive model. A total of 14 comparison studies from 11 articles met our inclusion criteria, comprising eight on SLE (1,284 patients and 1,885 controls) and four on RA (820 patients and 772 controls), and three studies investigated response to methotrexate (MTX) in RA according to the HLA-G 14 bp I/D polymorphisms (249 responders and 205 nonresponders). Meta-analysis revealed an association between the II + ID genotype of the HLA-G 14 bp I/D polymorphism in overall group (OR = 1.205, 95 % CI = 1.036–1.403, P = 0.016). Ethnicity-specific meta-analysis showed no association between the II + ID genotype and SLE in the South American, European, and Asian population. Meta-analysis revealed a significant association between SLE and the HLA-G +3142 G allele in all study subjects (OR = 1.367, 95 % CI = 1.158–1.613, P = 2.2 × 10−5) and in the South American group (OR = 1.531, 95 % CI = 1.242–1.888, P = 6.7 × 10−5). However, no association between HLA-G 14 bp I/D, and +3142 G/C polymorphisms and RA was found (OR for HLA-G I allele = 1.013, 95 % CI = 0.879–1.167, P = 0.859; OR for +3142 G allele = 0.980, 95 % CI = 0.742–1.294, P = 0.888). Furthermore, HLA-G 14 bp I/D polymorphism was not found to be associated with response to MTX in RA. This meta-analysis demonstrates that the HLA-G 14 bp I/D polymorphism is associated with susceptibility to SLE, and HLA-G +3142 G/C polymorphisms are associated with susceptibility to SLE in South Americans.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Lee YH, Nath SK (2005) Systemic lupus erythematosus susceptibility loci defined by genome scan meta-analysis. Hum Genet 118(3–4):434–443

    Article  PubMed  Google Scholar 

  2. Choi SJ, Rho YH, Ji JD, Song GG, Lee YH (2006) Genome scan meta-analysis of rheumatoid arthritis. Rheumatology (Oxford) 45(2):166–170

    Article  CAS  Google Scholar 

  3. Dorling A, Monk NJ, Lechler RI (2000) HLA-G inhibits the transendothelial migration of human NK cells. Eur J Immunol 30(2):586–593

    Article  CAS  PubMed  Google Scholar 

  4. Bainbridge DR, Ellis SA, Sargent IL (2000) HLA-G suppresses proliferation of CD4(+) T-lymphocytes. J Reprod Immunol 48(1):17–26

    Article  CAS  PubMed  Google Scholar 

  5. Rousseau P, Le Discorde M, Mouillot G, Marcou C, Carosella ED, Moreau P (2003) The 14 bp deletion-insertion polymorphism in the 3′ UT region of the HLA-G gene influences HLA-G mRNA stability. Hum Immunol 64(11):1005–1010

    Article  CAS  PubMed  Google Scholar 

  6. Tan Z, Randall G, Fan J, Camoretti-Mercado B, Brockman-Schneider R, Pan L et al (2007) Allele-specific targeting of microRNAs to HLA-G and risk of asthma. Am J Hum Genet 81(4):829–834

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Chen T, Lin J, Jin S, Ma S, Yu L, Huang K et al (2014) Association of three polymorphisms in the 3′ untranslated region of the HLA-G gene with systemic lupus erythematosus in a population from Yunnan. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 31(2):228–232

    CAS  PubMed  Google Scholar 

  8. Lucena-Silva N, de Souza VS, Gomes RG, Fantinatti A, Muniz YC, de Albuquerque RS et al (2013) HLA-G 3′ untranslated region polymorphisms are associated with systemic lupus erythematosus in 2 Brazilian populations. J Rheumatol 40(7):1104–1113

    Article  CAS  PubMed  Google Scholar 

  9. Consiglio CR, Veit TD, Monticielo OA, Mucenic T, Xavier RM, Brenol JC et al (2011) Association of the HLA-G gene +3142C > G polymorphism with systemic lupus erythematosus. Tissue Antigens 77(6):540–545

    Article  CAS  PubMed  Google Scholar 

  10. Wu FX, Wu LJ, Luo XY, Tang Z, Yang MH, Xie CM et al (2009) Lack of association between HLA-G 14-bp polymorphism and systemic lupus erythematosus in a Han Chinese population. Lupus 18(14):1259–1266

    Article  CAS  PubMed  Google Scholar 

  11. Veit TD, Cordero EA, Mucenic T, Monticielo OA, Brenol JC, Xavier RM et al (2009) Association of the HLA-G 14 bp polymorphism with systemic lupus erythematosus. Lupus 18(5):424–430

    Article  CAS  PubMed  Google Scholar 

  12. Rizzo R, Hviid TV, Govoni M, Padovan M, Rubini M, Melchiorri L et al (2008) HLA-G genotype and HLA-G expression in systemic lupus erythematosus: HLA-G as a putative susceptibility gene in systemic lupus erythematosus. Tissue Antigens 71(6):520–529

    Article  CAS  PubMed  Google Scholar 

  13. Catamo E, Addobbati C, Segat L, Sotero Fragoso T, Domingues Barbosa A, Tavares Dantas A et al (2014) HLA-G gene polymorphisms associated with susceptibility to rheumatoid arthritis disease and its severity in Brazilian patients. Tissue Antigens 84(3):308–315

  14. Veit TD, de Lima CP, Cavalheiro LC, Callegari-Jacques SM, Brenol CV, Brenol JC et al (2014) HLA-G +3142 polymorphism as a susceptibility marker in two rheumatoid arthritis populations in Brazil. Tissue Antigens 83(4):260–266

    Article  CAS  PubMed  Google Scholar 

  15. Rizzo R, Rubini M, Govoni M, Padovan M, Melchiorri L, Stignani M et al (2006) HLA-G 14-bp polymorphism regulates the methotrexate response in rheumatoid arthritis. Pharmacogenet Genomics 16(9):615–623

    Article  CAS  PubMed  Google Scholar 

  16. Stamp LK, O’Donnell JL, Chapman PT, Barclay ML, Kennedy MA, Frampton CM et al (2009) Lack of association between HLA-G 14 bp insertion/deletion polymorphism and response to long-term therapy with methotrexate response in rheumatoid arthritis. Ann Rheum Dis 68(1):154–155

    Article  CAS  PubMed  Google Scholar 

  17. Kooloos WM, Wessels JA, van der Straaten T, Allaart CF, Huizinga TW, Guchelaar HJ (2010) Functional polymorphisms and methotrexate treatment outcome in recent-onset rheumatoid arthritis. Pharmacogenomics 11(2):163–175

    Article  CAS  PubMed  Google Scholar 

  18. Lee YH, Rho YH, Choi SJ, Ji JD, Song GG (2007) PADI4 polymorphisms and rheumatoid arthritis susceptibility: a meta-analysis. Rheumatol Int 27(9):827–833

    Article  CAS  PubMed  Google Scholar 

  19. Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2011) Associations between vitamin D receptor polymorphisms and susceptibility to rheumatoid arthritis and systemic lupus erythematosus: a meta-analysis. Mol Biol Rep 38(6):3643–3651

    Article  CAS  PubMed  Google Scholar 

  20. Lee YH, Bae SC, Choi SJ, Ji JD, Song GG (2012) The association between the PTPN22 C1858T polymorphism and rheumatoid arthritis: a meta-analysis update. Mol Biol Rep 39(4):3453–3460

    Article  CAS  PubMed  Google Scholar 

  21. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  PubMed  Google Scholar 

  22. Egger M, Smith GD, Phillips AN (1997) Meta-analysis: principles and procedures. BMJ 315(7121):1533–1537

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  PubMed  Google Scholar 

  24. Faul F, Erdfelder E, Buchner A, Lang AG (2009) Statistical power analyses using G*Power 3.1: tests for correlation and regression analyses. Behav Res Methods 41(4):1149–1160

    Article  PubMed  Google Scholar 

  25. Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Carosella ED, Moreau P, Aractingi S, Rouas-Freiss N (2001) HLA-G: a shield against inflammatory aggression. Trends Immunol 22(10):553–555

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported in part by a Grant of the Korea Healthcare technology R&D Project, Ministry for Health and Welfare, Republic of Korea (HI13C2124).

Conflict of interest

The authors have no financial or nonfinancial conflict of interest to declare.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Young Ho Lee.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, Y.H., Bae, SC. & Song, G.G. Meta-analysis of associations between functional HLA-G polymorphisms and susceptibility to systemic lupus erythematosus and rheumatoid arthritis. Rheumatol Int 35, 953–961 (2015). https://doi.org/10.1007/s00296-014-3155-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00296-014-3155-3

Keywords

Navigation