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Meta-analysis of the association between functional MICA-TM polymorphisms and systemic lupus erythematosus, rheumatoid arthritis and ankylosing spondylitis

Metaanalyse des Zusammenhangs zwischen funktionell wirksamen MICA-TM-Polymorphismen und systemischem Lupus erythematodes, rheumatoider Arthritis sowie ankylosierender Spondylitis

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Abstract

Objective

The aim of this study was to determine whether the major histocompatibility complex class I chain-related gene A transmembrane (MICA-TM) polymorphism is associated with susceptibility to systemic lupus erythematous (SLE), rheumatoid arthritis (RA) and ankylosing spondylitis (AS).

Methods

A meta-analysis was conducted to establish the association between MICA-TM polymorphisms and SLE, RA and AS in the overall study population, as well as in each ethnic group.

Results

A total of 13 comparison studies, including five SLE (1601 patients; 1846 controls), four RA (701 patients; 887 controls) and four AS (346 patients; 356 controls) studies were considered in the meta-analysis. An association between the MICA-TM A5.1 allele and SLE was demonstrated in Europeans but not in Asians: odds ratio (OR) = 1.699, 95 % confidence interval (CI) = 1.123–2.569, p = 0.012 and OR = 0.949, 95 % CI = 0.502–1.793, p = 0.871, respectively. However, no association was found in Europeans after Bonferroni correction (pcorrected = 0.060). An association was found between the MICA-TM A9 allele and RA in Asians (OR = 0.527, 95 % CI = 0.408–0.681, p = 8.9 × 10−7) but not in Europeans; the association in Asians remained significant after Bonferroni correction (pcorrected = 4.5 × 10−6). An association between the MICA-TM A4 phenotype and AS was observed in European and Asian populations (OR = 12.87, 95 % CI = 6.747–24.58, p < 1.0 × 10−9 and OR = 9.461, 95 % CI = 5.754–15.55, p < 1.0 × 10−9, respectively). Meta-analysis stratified by human leukocyte antigen (HLA)-B27 status revealed an association between the MICA-TM A4 phenotype and HLA-B27 positivity AS in Asians, but not in Europeans (OR = 0.318, 95 % CI = 0.102–0.995, p = 0.049 and OR = 2.080, 95 % CI = 0.422–10.25, p = 0.368, respectively). However, the association in Asians was not significant after Bonferroni correction (pcorrected = 0.245).

Conclusion

This meta-analysis demonstrated that there was no association between MICA-TM polymorphisms and SLE susceptibility, but that the MICA-TM A9 allele was associated with an RA risk in Asians. Moreover, the association between the MICA-TM A4 phenotype and AS was HLA-B27-dependent.

Zusammenfassung

Ziel

Ziel der vorliegenden Studie war zu untersuchen, ob der MICA-TM-Polymorphismus (MICA: „major histocompatibility complex class I chain-related gene A“, MHC-Klasse-I-assoziiertes Gen A; TM-: Transmembran-) mit der Anfälligkeit für systemischen Lupus erythematodes (SLE), rheumatoide Arthritis (RA) und ankylosierende Spondylitis (AS) in Zusammenhang steht.

Methoden

Es wurde eine Metaanalyse durchgeführt, um den Zusammenhang zwischen MICA-TM-Polymorphismen und SLE, RA sowie AS sowohl in der gesamten Studienpopulation als auch in den einzelnen ethnischen Gruppen zu untersuchen.

Ergebnisse

In der Metaanalyse wurden 13 Vergleichsstudien, davon 5 zu SLE (1601 Patienten, 1846 Kontrollen), 4 zu RA (701 Patienten, 887 Kontrollen) und 4 zu AS (346 Patienten, 356 Kontrollen) ausgewertet. Ein Zusammenhang zwischen dem MICA-TM-A5.1-Allel und SLE wurde bei Europäern, nicht aber bei Asiaten festgestellt: Odds Ratio (OR): 1,699; 95%-Konfidenzintervall (95%-KI): 1,123–2,569; p = 0,012 bzw. OR: 0,949; 95%-KI: 0,502–1,793; p = 0,871. Jedoch bestand kein Zusammenhang für Europäer nach Bonferroni-Korrektur (pcorrected = 0,060). Zwischen dem MICA-TM-A9-Allel und RA wurde bei Asiaten (OR: 0,527; 95%-KI: 0,408–0,681; p = 8,9 × 10−7), nicht aber bei Europäern ein Zusammenhang nachgewiesen; der Zusammenhang blieb auch nach Bonferroni-Korrektur signifikant (pcorrected = 4,5 × 10−6). Einen Zusammenhang gab es zwischen dem MICA-TM-A4-Phänotyp und AS in europäischen und asiatischen Populationen (OR: 12,87; 95%-KI: 6,747–24,58; p < 1,0 × 10−9 bzw. OR: 9,461; 95%-KI: 5,754–15,55; p < 1,0 × 10−9). Bei Stratifizierung der Metaanalyse gemäß dem Status beim humanen Leukozytenantigen (HLA-)B27 zeigte sich ein Zusammenhang zwischen dem MICA-TM-A4-Phänotyp und HLA-B27-Positivität bei AS für Asiaten, nicht aber für Europäer (OR: 0,318; 95%-KI: 0,102–0,995; p = 0,049 bzw. OR: 2,080; 95%-KI: 0,422–10,25; p = 0,368). Allerdings war der Zusammenhang bei Asiaten nach Bonferroni-Korrektur nicht signifikant (pcorrected = 0,245).

Schlussfolgerung

Diese Metaanalyse hat gezeigt, dass es zwar keinen Zusammenhang zwischen MICA-TM-Polymorphismen und SLE-Anfälligkeit gab, aber dass das MICA-TM-A9-Allel mit einem RA-Risiko bei Asiaten assoziiert war. Darüber hinaus war der Zusammenhang zwischen dem MICA-TM-A4-Phänotyp und AS vom HLA-B27-Status abhängig.

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Acknowledgements

This study was supported in part by a grant of the Korea Healthcare technology R&D project, Ministry for Health & Welfare, Republic of Korea (HI12C1834).

Compliance with ethical guidelines

Conflict of interest. Y.H. Lee, S.-C. Bae, 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

  2. Division of Rheumatology, Department of Internal Medicine, The Hospital for Rheumatic Diseases, Hanyang University Medical Center, Seoul, Korea

    S.-C. Bae

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  1. Y.H. Lee MD, PhD
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Correspondence to Y.H. Lee MD, PhD.

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Lee, Y., Bae, SC., Kim, JH. et al. Meta-analysis of the association between functional MICA-TM polymorphisms and systemic lupus erythematosus, rheumatoid arthritis and ankylosing spondylitis. Z. Rheumatol. 74, 146–152 (2015). https://doi.org/10.1007/s00393-014-1409-9

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  • DOI: https://doi.org/10.1007/s00393-014-1409-9

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