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Association between IRAK1 rs3027898 and miRNA-499 rs3746444 polymorphisms and rheumatoid arthritis

A case control study and meta-analysis

Assoziation zwischen Polymorphismen von IRAK1 rs3027898 und miRNA-499 rs3746444 und rheumatoider Arthritis

Eine Fall-Kontroll-Studie und Metaanalyse

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Abstract

Background

The IRAK1 and miR-499 polymorphisms play an important role in the etiology of rheumatoid arthritis (RA). Several studies have been carried out to estimate the association between IRAK1 rs3027898 and miR-499 rs3746444 and RA risk; however, the results were inconsistent.

Aim

A case control study was carried out to explore the association between IRAK1 rs3027898 and miR-499 rs3746444 and the RA risk in a Chinese population. Meta-analyses combining present with previous studies were conducted to further explore the association.

Material and methods

A total of 386 RA patients were enrolled along with 576 matched healthy controls. Genotyping was performed by using TaqMan genotyping assays on Fluidigm 192.24 system. For the meta-analysis, a systematic literature search was conducted to identify all relevant studies.

Results

This case control study showed that the IRAK1 rs3027898 C allele was associated with increased risk of RA with an odds ratio (OR) = 1.4 and 95 % confidence intervals (CI) = 1.093–1.793, P = 0.008 but miR-499 rs3746444 polymorphisms were not significantly associated with the risk for RA. The meta-analyses included a total of 4 case control studies on IRAK1 rs3027898 and 4 studies on miR-499 rs3746444. The IRAK1 rs3027898 C allele had an overall OR of 1.268 (95 % CI = 1.130–1.424, P < 0.001). After stratification by ethnicity the C allele had an OR of 1.238 (95 % CI = 1.096–1.398, P = 0.001) in Asians. No association between miR-499 rs3746444 polymorphism and RA was found in the overall and Asian populations.

Conclusion

The results from our case control study and the meta-analyses indicate that the IRAK1 rs3027898 C allele is significantly associated with an increased risk of RA, especially in Asians.

Zusammenfassung

Hintergrund

Die Polymorphismen von IRAK1 und miR-499 spielen eine wichtige Rolle in der Ätiologie der rheumatoiden Arthritis (RA). In mehreren Studien wurde ein Zusammenhang zwischen IRAK1 rs3027898 und miR-499 rs3746444 und dem Risiko einer RA angenommen, die Ergebnisse waren jedoch widersprüchlich.

Ziel

Bei einer chinesischen Population wurde eine Fall-Kontroll-Studie zur Beurteilung der Assoziation zwischen IRAK1 rs3027898 und miR-499 rs3746444 und dem Risiko einer RA durchgeführt. Es erfolgten Metaanalysen, die aktuelle mit früheren Studien kombinierten, um diesen Zusammenhang weiter zu untersuchen.

Materialien und Methoden

Insgesamt 386 RA-Patienten sowie 576 gematchte gesunde Kontrollpersonen wurden eingeschlossen. Die Genotypisierung erfolgte mit Hilfe der TaqMan-Genotyping-Assays mit dem Fluidigm-192.24-System. Für die Metaanalyse wurde eine systematische Literaturrecherche durchgeführt, um alle relevanten Studien zu identifizieren.

Ergebnisse

Die Fall-Kontroll-Studie zeigte, dass das C‑Allel von IRAK1-rs3027898 mit einem erhöhten Risiko für RA assoziiert war (Odds-Ratio [OR] = 1,4, 95 % Konfidenzintervall [CI] = 1,093–1,793; P = 0,008). Polymorphismen von miR-499 rs3746444 waren jedoch nicht signifikant mit dem Risiko für eine RA assoziiert. Die Metaanalyse schloss insgesamt 4 Fall-Kontroll-Studien zu IRAK1 rs3027898 und 4 Studien zu miR-499 rs3746444 ein. Die Gesamt-OR für das C‑Allel von IRAK1-rs3027898 betrug 1,268 (95 % CI = 1,130–1,424; p < 0,001). Nach der Stratifizierung nach Ethnizität betrug die OR für das C‑Allel 1,238 (95 % CI = 1,096–1,398; P = 0,001) bei Asiaten. Es wurde bei der gesamten asiatischen Population kein Zusammenhang zwischen dem Polymorphismus von miR-499 rs3746444 und RA festgestellt.

Schlussfolgerung

Die Ergebnisse dieser Fall-Kontroll-Studie und der Metaanalyse zeigen, dass das C‑Allel von IRAK1-rs3027898 signifikant mit einem erhöhten Risiko für RA assoziiert ist, insbesondere bei Asiaten.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81473058).

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, 230032, Hefei, Anhui, China

    X.-K. Yang, P. Li, C. Zhang, R.-X. Leng, J. Liu, B.-Z. Li, H.-F. Pan & D.-Q. Ye M.D.

  2. Anhui Provincial Laboratory of Population Health & Major Disease Screening and Diagnosis, Anhui Medical University, Hefei, Anhui, China

    X.-K. Yang, P. Li, C. Zhang, R.-X. Leng, J. Liu, B.-Z. Li, H.-F. Pan & D.-Q. Ye M.D.

  3. ChaoHu Hospital, Anhui Medical University, Hefei, Anhui, China

    S. Li

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Correspondence to D.-Q. Ye M.D..

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Conflict of interests

X.-K. Yang, P. Li, C. Zhang, R.‑X. Leng, S. Li, J. Liu, B.‑Z. Li, H.‑F. Pan and D.‑Q. Ye declare that they have no conflict of interests.

All studies on humans described in the present manuscript were carried out with the approval of the responsible ethics committee and in accordance with national law and the Helsinki Declaration of 1975 (in its current revised form). Informed consent was obtained from all participants included in the study.

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Yang, XK., Li, P., Zhang, C. et al. Association between IRAK1 rs3027898 and miRNA-499 rs3746444 polymorphisms and rheumatoid arthritis. Z Rheumatol 76, 622–629 (2017). https://doi.org/10.1007/s00393-016-0169-0

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