Zeitschrift für Rheumatologie

, Volume 74, Issue 3, pp 230–239 | Cite as

Meta-analysis of genetic polymorphisms in programmed cell death 1

Associations with rheumatoid arthritis, ankylosing spondylitis, and type 1 diabetes susceptibility
Originalien
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Abstract

Objective

The aim of this study was to determine whether genetic polymorphisms in programmed cell death 1 (PDCD1 or PD1) are associated with susceptibility to rheumatoid arthritis (RA), ankylosing spondylitis (AS), and type 1 diabetes (T1D).

Methods

We conducted a meta-analysis to investigate the association between PDCD1 polymorphisms and RA, AS, and T1D in the overall population and in specific ethnic populations.

Results

Sixteen studies, comprising 13,210 patients and 17,073 controls, were conducted for the meta-analysis including 4 studies on RA, 4 on AS, and 8 on T1D. The meta-analysis showed an association between RA and the 2 alleles of the PD1.3 polymorphism in the overall population [odds ratio (OR) 1.183, 95 % confidence interval (95 % CI) 1.005–1.392, p = 0.043]. However, meta-analysis showed no association between RA and the 2 alleles of the PD1.1 and PD1.5 polymorphisms in the overall population. Meta-analysis identified an association between AS and the 2 alleles of the PD1.5 and PD1.9 polymorphisms in the Asian population (OR 1.251, 95 % CI 1.019–1.535, p = 0.033; OR 1.975, 95 % CI 1.286–3.034, p = 0.002, respectively). The meta-analysis revealed a significant association between T1D and the 2 alleles of the PD1.3 polymorphism in the European population (OR 1.098, 95 % CI 1.029–1.171, p = 0.005). The meta-analysis showed an association between the PD1.5 polymorphism and T1D in Asians (OR 1.332, 95 % CI 1.067–1.663, p = 0.011) and between the PD1.9 polymorphism and T1D in the Asian population (OR 1.363, 95 % CI 1.107–1.679, p = 0.004).

Conclusion

The meta-analysis suggests an association between the PD1.3 polymorphism and RA in the overall population and an association between the PD1.5 and PD1.9 polymorphisms, and AS in the Asian population. Furthermore, the PD1.3 , 5, and 9 polymorphisms were associated with T1D susceptibility in Europeans, or Asians.

Keywords

Inflammation Autoimmune diseases Gene frequency Apoptosis Peripheral tolerance 

Metaanalyse von Genpolymorphismen beim programmierten Zelltod 1

Assoziationen mit der Suzeptibiliät für rheumatoide Arthritis, ankylosierende Spondylitis und Typ-1-Diabetes

Zusammenfassung

Ziel

Ziel der Studie war es zu überprüfen, ob ein Zusammenhang zwischen genetischen Polymorphismen beim programmierten Zelltod (PDCD1 oder PD1) und der Suszeptibilität für rheumatoide Arthritis (RA), ankylosierende Spondylitis (AS) und Typ-1-Diabetes (T1D) besteht.

Methoden

Zur Überprüfung der Assoziation zwischen PDCD1-Polymorphismen und RA, AS bzw. T1D im Gesamtkollektiv und in nach ethnischer Zugehörigkeit gebildeten Subkollektiven wurde eine Metaanalyse durchgeführt.

Ergebnisse

In die Metaanalyse wurden insgesamt 16 Studien (4 zu RA, 4 zu AS und 8 zu T1D) mit 13.210 Patienten und 17.073 Kontrollen aufgenommen. Im Gesamtkollektiv fand sich eine Assoziation zwischen RA und den 2 Allelen des PD1.3-Polymorphismus im Gesamtkollektiv [Odds Ratio (OR) 1,183, 95 %-Konfidenzintervall (KI) 1,005–1,392, p = 0,043], allerdings keine Assoziation zwischen RA und den 2 Allelen der PD1,1- und PD1,5-Polymorphismen. Die Metaanalyse identifizierte eine Assoziation zwischen AS und den 2 Allelen der PD1,5- und PD1,9-Polymorphismen im asiatischen Kollektiv (OR 1,251, 95 %-KI 1,019–1,535, p = 0,033 bzw. OR 1,975, 95 %-KI 1,286–3.034, p = 0,002). Sie zeigte im europäischen Kollektiv eine signifikante Assoziation zwischen T1D und den 2 Allelen des PD1,3-Polymorphismus (OR 1,098, 95 %-KI 1,029–1,171, p = 0,005). Ferner fanden sich im asiatischen Kollektiv Assoziationen zwischen dem PD1,5-Polymorphismus und T1D (OR 1,332, 95 %-KI 1,067–1,663, p = 0,011) sowie zwischen dem PD1,9-Polymorphismus und T1D (OR 1,363, 95 %-KI 1,107–1,679, p = 0,004).

Fazit

Die Metaanalyse weist auf einen Zusammenhang zwischen dem PD1.3-Polymorphismus und RA im Gesamtkollektiv hin sowie auf einen Zusammenhang zwischen den PD1.5- und PD1.9-Polymorphismen und AS im asiatischen Subkollektiv. Ferner waren die PD1.3- , - 5-, und -9-Polymorphismen assoziiert mit einer T1D-Suszeptibilität bei Europäern bzw. Asiaten

Schlüsselwörter

Inflammation Autoimmunerkrankungen Genhäufigkeit Apoptose Periphere Immuntoleranz 
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Notes

Acknowledgments

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Division of Rheumatology, Department of Internal MedicineKorea University Anam Hospital, Korea University College of MedicineSeoulKorea
  2. 2.The Hospital for Autoimmune DiseasesHanyang University Medical CenterSeoulKorea

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