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The association between susceptibility to inflammatory arthritis and miR-146a, miR-499 and IRAK1 polymorphisms

A meta-analysis

Suszeptibilität für inflammatorische Arthritis und miR-146a, miR-499 and IRAK1-Polymorphismen

Eine Metaanalyse

Abstract

Objective

The aim of this study was to explore whether polymorphisms in miR-146a, miR-499 and IRAK1 are associated with susceptibility to inflammatory arthritis.

Methods

Manual searches performed in the MEDLINE and EMBASE databases were used to identify published articles in which the roles of microRNA (miRNA) and IRAK1 polymorphisms in inflammatory arthritis were determined. A meta-analysis was conducted to investigate associations of the miR-146a rs2910164, miR-499 rs3746444, IRAK1 rs3027898 and IRAK1 rs1059703 polymorphisms with susceptibility to inflammatory arthritis.

Results

Nine studies containing 1224 patients and 1841 controls were included in the meta-analysis. The meta-analysis revealed no association between inflammatory arthritis and the rs2910164 C allele of miR-146a (odds ratio, OR = 0.974; 95 % confidence interval, CI = 0.810–1.091; p = 0.650). Stratification by ethnicity or disease type revealed no association between the miR-146a C allele and inflammatory arthritis in European, Middle Eastern or Asian patients with rheumatoid arthritis (RA) or juvenile idiopathic arthritis (JIA). However, the meta-analysis revealed an overall association between RA and the miR-499 rs374644 C (OR = 1.123, 95 % CI = 1.019–2.586, p = 0.041); stratification by ethnicity revealed a particular association in Middle Eastern populations (OR = 1.943, 95 % CI = 1.508–2.504, p = 2.7 × 10–8). The meta-analysis of IRAK1 polymorphisms revealed an association between inflammatory arthritis and the rs3027898 CC genotype (OR = 2.602, 95 % CI = 1.387–4.879, p = 0.003). An analysis using the homozygote contrast showed the same pattern for the rs3027898 CC genotype (OR = 2.472, 95 % CI = 1.300–4.700, p = 0.006). No association between inflammatory arthritis and the rs1059703 polymorphism was found.

Conclusion

This meta-analysis suggests that the miR-499 rs374644 and IRAKI rs3027898 polymorphisms are associated with susceptibility to inflammatory arthritis.

Zusammenfassung

Ziel

Ziel der Studie war die Erforschung möglicher Zusammenhänge zwischen Polymorphismen in den Genen miR-146a, miR-499 und IRAK1 mit der Suszeptibilität für inflammatorische Arthritiden.

Methoden

Manuell wurde in den Datenbanken MEDLINE und EMBASE nach Veröffentlichungen zur Rolle von microRNA(miRNA)- und IRAK1-Polymorphismen bei inflammatorischer Arthritis gesucht. Zur Überprüfung von Assoziationen zwischen miR-146a rs2910164-, miR-499 rs3746444-, IRAK1 rs3027898- und IRAK1 rs1059703-Polymorphismen und der Suszeptibilität für inflammatorische Arthritis wurde eine Metaanalyse durchgeführt.

Ergebnisse

Neun Studien mit 1224 Patienten und 1841 Kontrollen wurden in die Metaanalyse aufgenommen. Die Metaanalyse zeigte keine Assoziation zwischen inflammatorischer Arthritis und dem rs2910164 C-Allel von miR-146a (Odds Ratio, OR,= 0,974; 95 %-Konfidenzintervall, 95%-KI = 0,810–1,091; p = 0,650). Die Stratifizierung nach Ethnizität bzw. Erkrankungstyp ergab keine Assoziation zwischen dem miR-146a C-Allel und inflammatorischer Arthritis bei Patienten aus Europa, dem nahen Osten und Asien mit rheumatoider Arthritis (RA) bzw. juveniler idiopathischer Arthritis (JIA). Doch die Metaanalyse deckte einen Zusammenhang insgesamt auf zwischen RA und miR-499 rs374644 C (OR = 1,123, 95 %-KI = 1,019–2,586, p = 0,041) und die Stratifizierung nach Ethnizität eine besondere Assoziation im Nahostkollektiven (OR = 1,943, 95 %-KI = 1,508–2,504, p = 2,7 × 10–8). Die Metaanalyse von IRAK1 –Polymorphismen zeigte eine Assoziation zwischen inflammatorischer Arthritis und dem rs3027898 CC-Genotyp (OR = 2,602, 95 %-KI = 1,387–4,879, p = 0,003). Eine Analyse unter Verwendung von „homozygote contrast“ ergab das gleiche Muster für den rs3027898 CC-Genotyp (OR = 2,472, 95 %-KI = 1,300–4,700, p = 0,006). Keine Assoziation fand sich zwischen inflammatorischer Arthritis und dem rs1059703-Polymorphismus.

Fazit

Die Metaanalyse verweist auf einen Zusammenhang zwischen den miR-499 rs374644- und IRAKI rs3027898-Polymorphismen und der Suszeptibilität für inflammatorische Arthritis.

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Acknowledgement

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).

Compliance with ethical guidelines

Conflict of interest. G.G. Song, S.-C. Bae, Y. H. Seo, J.-H. Kim, S. J. Choi, J. D. Ji and Y.Ho. Lee state that there are no conflicts of interest. The accompanying manuscript does not include studies on humans or animals.

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Correspondence to Y.H. Lee MD, PhD.

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Song, G., Bae, SC., Seo, Y. et al. The association between susceptibility to inflammatory arthritis and miR-146a, miR-499 and IRAK1 polymorphisms. Z Rheumatol 74, 637–645 (2015). https://doi.org/10.1007/s00393-014-1493-x

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  • DOI: https://doi.org/10.1007/s00393-014-1493-x

Keywords

  • Rheumatoid arthritis
  • MicroRNA
  • MEDLINE
  • Ethnicity
  • Genotype

Schlüsselwörter

  • Rheumatoide Arthritis
  • Micro-RNA
  • MEDLINE
  • Ethnizität
  • Genotyp