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Associations between major histocompatibility complex class I chain-related gene A polymorphisms and susceptibility to Behcet’s disease

A meta-analysis

Assoziation zwischen Haupthistokompatibilitätskomplex-Klasse-I-Ketten-bezogenen Gen-A-Polymorphismen und der Suszeptibilität für M. Beçet

Eine Metaanalyse

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Abstract

Objective

The purpose of this work was to investigate whether major histocompatibility complex class I chain-related gene A (MICA) polymorphisms are associated with susceptibility to Behcet’s disease (BD).

Methods

A meta-analysis was conducted on the associations between the MICA-transmembrane (TM) A6 allele and the 009 allele of MICA exon 2–4 (MICA*009) and BD with or without HLA-B51 overall and in each ethnic group.

Results

Fifteen comparison studies were included in this meta-analysis. The meta-analysis revealed a significant association between the MICA-TM A6 allele and BD in European, Asian, and Arab populations [odds ratio (OR) 1.436, 95 % confidence interval (CI) 1.111–1.857, p = 0.006; OR 1.999, 95 % CI 1.551–2.575, p = 8.0 × 10−8; OR 1.333, 95 % CI 1.058–2.300, p = 0.025, respectively,]). Stratification by HLA-B51 showed an association between the MICA-TM A6 allele and BD with HLA-B51 in the overall group and in the European population. Meta-analysis showed a significant association between the MICA*009 allele and BD in the overall group (OR 3.948, 95 % CI 2.680–5.815, p < 1.0 × 10−8) and in the European population (OR 3.392, 95 % CI 2.118–5.433, p = 5.6 × 10−6). A significant association was found between the MICA*009 allele and B51-positive BD.

Conclusion

This meta-analysis shows that the MICA-TM A6 allele and the MICA*009 allele are associated with BD susceptibility in various ethnic populations, and that MICA alleles are in strong linkage disequilibrium with HLA-B51 in BD.

Zusammenfassung

Ziel

Ziel dieser Arbeit war es, zu untersuchen, ob Polymorphismen im Haupthistokompatibilitätskomplex-Klasse-I-Ketten-bezogenen Gen-A (MICA) mit einer Suszeptibilität für M. Beçet („Beçet’s disease“, BD) assoziiert sind.

Methoden

Es wurde eine Metaanalyse zur Assoziation zwischen dem MICA-Transmembran(TM)-A6-Allel sowie dem 009-Allel des MICA-Exons 2–4 (MICA*009) und BD mit oder ohne HLA-B51 in der Gesamtgruppe sowie in jeder einzelnen ethnischen Gruppe durchgeführt.

Ergebnisse

Fünfzehn Vergleichsstudien wurden in die Metaanalyse eingeschlossen. Die Metaanalyse zeigte eine signifikante Assoziation zwischen dem MICA-TM-A6-Allel und BD in europäischen, asiatischen und arabischen Populationen [Odds-Ratio (OR) 1,436; 95 % Konfidenzintervall (CI) 1,111–1,857; p = 0,006; OR 1,999; 95 % CI 1,551–2,575; p = 8,0 × 10−8; OR 1,333; 95 % CI 1,058–2,300; p = 0,025]. In einer Stratifizierung nach HLA-B51 wurde eine Assoziation zwischen dem MICA-TM-A6-Allel und BD mit HLA-B51 in der Gesamtgruppe sowie in der europäischen Population festgestellt. Die Metaanalyse zeigte eine signifikante Assoziation zwischen dem MICA*009-Allel und BD in der Gesamtgruppe (OR 3,948; 95 % CI 2,680–5,815; p < 1,0 × 10−8) sowie in der europäischen Population (OR 3,392; 95 % CI 2,118–5,433; p = 5,6 × 10−6). Eine signifikante Assoziation wurde zwischen dem MICA*009-Allel und B51-positiver BD gefunden.

Schlussfolgerung

Diese Metaanalyse zeigt, dass das MICA-TM-A6-Allel und das MICA*009-Allel in verschiedenen ethnischen Populationen mit einer Suszeptibilität für BD assoziiert sind, und dass bei MICA-Allelen ein starkes Ungleichgewicht in Verbindung mit HLA-B51 bei BD besteht.

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References

  1. Sakane T, Takeno M, Suzuki N (1999) Inaba G. Behcet’s disease. N Engl J Med 341(17):1284–1291

    Article  CAS  PubMed  Google Scholar 

  2. Criteria for diagnosis of Behcet’s disease (1990) International Study Group for Behcet’s Disease. Lancet 335(8697):1078–1080

    Google Scholar 

  3. Groh V, Steinle A, Bauer S, Spies T (1998) Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells. Science 279(5357):1737–1740

    Article  CAS  PubMed  Google Scholar 

  4. Zwirner NW, Fernandez-Vina MA, Stastny P (1998) MICA, a new polymorphic HLA-related antigen, is expressed mainly by keratinocytes, endothelial cells, and monocytes. Immunogenetics 47(2):139–148

    Article  CAS  PubMed  Google Scholar 

  5. Bahram S, Bresnahan M, Geraghty DE, Spies T (1994) A second lineage of mammalian major histocompatibility complex class I genes. Proc Natl Acad Sci U S A 91(14):6259–6263

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Rueda B, Pascual M, Lopez-Nevot MA et al (2002) A new allele within the transmembrane region of the human MICA gene with seven GCT repeats. Tissue Antigens 60(6):526–528

    Article  CAS  PubMed  Google Scholar 

  7. Mizuki N, Ota M, Kimura M et al (1997) Triplet repeat polymorphism in the transmembrane region of the MICA gene: a strong association of six GCT repetitions with Behcet disease. Proc Natl Acad Sci U S A 94(4):1298–1303

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Mizuki N, Meguro A, Tohnai I et al (2007) Association of major histocompatibility complex class i chain-related gene A and HLA-B alleles with Behcet’s disease in Turkey. Jpn J Ophthalmol 51(6):431–436

    Article  PubMed  Google Scholar 

  9. Munoz-Saa I, Cambra A, Pallares L et al (2006) Allelic diversity and affinity variants of MICA are imbalanced in Spanish patients with Behcet’s disease. Scand J Immunol 64(1):77–82

    Article  CAS  PubMed  Google Scholar 

  10. Nishiyama M, Takahashi M, Manaka K et al (2006) Microsatellite polymorphisms of the MICA gene among Japanese patients with Behcet’s disease. Can J Ophthalmol 41(2):210–215

    Article  PubMed  Google Scholar 

  11. Hughes EH, Collins RW, Kondeatis E et al (2005) Associations of major histocompatibility complex class I chain-related molecule polymorphisms with Behcet’s disease in Caucasian patients. Tissue Antigens 66(3):195–199

    Article  CAS  PubMed  Google Scholar 

  12. Mizuki N, Yabuki K, Ota M et al (2002) Analysis of microsatellite polymorphism around the HLA-B locus in Iranian patients with Behcet’s disease. Tissue Antigens 60(5):396–399

    Article  CAS  PubMed  Google Scholar 

  13. Picco P, Porfirio B, Gattorno M et al (2002) MICA gene polymorphisms in an Italian paediatric series of juvenile Behcet disease. Int J Mol Med 10(5):575–578

    CAS  PubMed  Google Scholar 

  14. Park SH, Park KS, Seo YI et al (2002) Association of MICA polymorphism with HLA-B51 and disease severity in Korean patients with Behcet’s disease. J Korean Med Sci 17(3):366–370

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Mizuki N, Ota M, Yabuki K et al (2000) Localization of the pathogenic gene of Behcet’s disease by microsatellite analysis of three different populations. Invest Ophthalmol Vis Sci 41(12):3702–3708

    CAS  PubMed  Google Scholar 

  16. Gonzalez-Escribano MF, Rodriguez MR, Aguilar F et al (1999) Lack of association of MICA transmembrane region polymorphism and Behcet’s disease in Spain. Tissue Antigens 54(3):278–281

    Article  CAS  PubMed  Google Scholar 

  17. Yabuki K, Mizuki N, Ota M et al (1999) Association of MICA gene and HLA-B*5101 with Behcet’s disease in Greece. Invest Ophthalmol Vis Sci 40(9):1921–1926

    CAS  PubMed  Google Scholar 

  18. Salvarani C, Boiardi L, Mantovani V et al (2001) Association of MICA alleles and HLA-B51 in Italian patients with Behcet’s disease. J Rheumatol 28(8):1867–1870

    CAS  PubMed  Google Scholar 

  19. Cohen R, Metzger S, Nahir M, Chajek-Shaul T (2002) Association of the MIC-A gene and HLA-B51 with Behcet’s disease in Arabs and non-Ashkenazi Jews in Israel. Ann Rheum Dis 61(2):157–160

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Egger M, Davey Smith G, 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 

  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. Ota M, Mizuki N, Katsuyama Y et al (1999) The critical region for Behcet disease in the human major histocompatibility complex is reduced to a 46-kb segment centromeric of HLA-B, by association analysis using refined microsatellite mapping. Am J Hum Genet 64(5):1406–1410

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Nishiyama M, Takahashi M, Manaka K et al (2005) Clinical features of Japanese patients with Behcet’s disease and MICA polymorphism. Jpn J Ophthalmol 49(5):424–426

    Article  PubMed  Google Scholar 

  26. Ben Ahmed M, Houman H, Abdelhak S et al (2003) MICA transmembrane region polymorphism and HLA B51 in Tunisian Behcet’s disease patients. Adv Exp Med Biol 528:225–228

    Google Scholar 

  27. Groh V, Bahram S, Bauer S et al (1996) Cell stress-regulated human major histocompatibility complex class I gene expressed in gastrointestinal epithelium. Proc Natl Acad Sci U S A 93(22):12445–12450

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Hughes T, Coit P, Adler A et al (2013) Identification of multiple independent susceptibility loci in the HLA region in Behcet’s disease. Nat Genet 45(3):319–324

    Article  CAS  PubMed  Google Scholar 

  29. Song GG, Kim JH, Lee YH (2014) Associations between the major histocompatibility complex class I chain-related gene A transmembrane (MICA-TM) polymorphism and susceptibility to psoriasis and psoriatic arthritis: a meta-analysis. Rheumatol Int 34(1):117–123

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Compliance with ethical guidelines

Conflict of interest. Y.H. Lee 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 & G.G. Song

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

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Lee, Y., Song, G. Associations between major histocompatibility complex class I chain-related gene A polymorphisms and susceptibility to Behcet’s disease. Z Rheumatol 74, 714–721 (2015). https://doi.org/10.1007/s00393-014-1536-3

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  • DOI: https://doi.org/10.1007/s00393-014-1536-3

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