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The meta-analysis of the association of PPARG P12A, C161T polymorphism and coronary heart disease

Metaanalyse der Assoziation von PPARG P12A und C161T Polymorphismen und koronarer Herzkrankheit

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Summary

Objective

Two common variations of peroxisome proliferator-activated receptor γ (PPARG), P12A (Pro12Ala, rs1801282), and C161T (His447His, rs3856806), are thought to have an effect on susceptibility to coronary heart disease (CHD), but the results are inconsistent. Therefore, a meta-analysis of published studies was performed.

Methods

The electronic databases, PubMed, Embase, Web of Science, and CNKI (China National Knowledge Infrastructure) were searched for studies to include in the present meta-analysis (last search was updated on 30 Aug. 2011). Twenty studies testing the association between PPARG gene polymorphisms and CHD were examined: 12 studies of P12A; 8 studies of C161T. Overall and ethnicity-specific summary odds ratios and corresponding 95 % confidence intervals for CHD associated with these polymorphisms were estimated using fixed- and random-effects models. Heterogeneity and publication bias were evaluated. A total of 20 studies including 5,795 cases and 9,069 controls were included in this meta-analysis.

Results

No significant associations were found in carriers of the rare Ala allele of the P12A polymorphism versus the common Pro/Pro genotype among the studies with both of the fixed-effect and random-effect model. In the subgroup analyses by ethnicity, source of control and type of study, no significant risks were found. For PPARG C161T, carriers of the T variant of C161T polymorphism were associated with an increased risk of CHD (OR = 1.182, 95 % CI: 1.023–1.341, Pheterogeneity = 0.002), and in the stratified analysis by ethnicity and source of controls, the contrast of CT + TT vs. CC all produced significant association in Asian and hospital-based controls (OR = 1.276, 95 % CI: 1.084–1.468, Pheterogeneity = 0.055; OR = 1.164, 95 % CI: 1.001–1.326, Pheterogeneity = 0.002),when the fixed-effect model was used. But they were all insignificant with the random-effect model.

Conclusion

This meta-analysis suggests that the PPARG C161T polymorphism marginally contributes to increased susceptibility to CHD and marginally increased association between PPARG H477H polymorphism and CHD also appeared in Asian and hospital-based controls. But PPARG P12A polymorphism is not associated with CHD risk.

Zusammenfassung

Ziel der Studie

Von zwei häufigen Variationen des Peroxisomen Proliferator-aktivierten Rezeptors γ (PPARG), P12A (Pro12Ala, rs1801282) und C161T (His447His, rs3856806), wird vermutet, dass sie eine Auswirkung auf die Anfälligkeit, eine koronare Herzkrankheit (CHD) zu bekommen, haben. Die Ergebnisse sind allerdings widersprüchlich, weshalb eine Meta-Analyse der publizierten Studien durchgeführt wurde.

Methodik

Die elektronischen Datenbanken PubMed, Embase, Web of Science, und CNKI (China National Knowledge Infrastructure) wurden nach Studien zum Einschluss in die vorliegende Meta-Analyse untersucht (die letzte Suche wurde mit 30.8.2011 upgedatet). Es wurden 20 Studien, die den Zusammenhang zwischen PPARG Gen Polymorphismen und der CHD untersuchten, geprüft: zwölf bzgl. P12A und acht bzgl. C161T. Gesamt- und ethnisch spezifische Summary Odd Ratios und 95 % Konfidenz Intervalle für den Zusammenhang zwischen diesen Polymorphismen und einer CHD wurden mit Hilfe von fixen und Zufalls-Wirkungsmodellen errechnet. Die Studien wurden auf Heterogenität und mögliche Vorurteile geprüft. In diese Metaanalyse von 20 Studien wurden insgesamt 5.795 Patienten und 9.069 Kontrollen eingeschlossen.

Ergebnisse

Bei den Trägern des seltenen Ala Allels des P12A Polymorphismus wurden im Vergleich zum häufigen Pro/Pro Genotyp bei der Auswertung der Studien unter Verwendung beider statistischen Modelle keine signifikanten Assoziationen gefunden. Die Subgruppen-Analyse auf Volkszugehörigkeit, auf Zusammensetzung der Kontrolle und auf Art der Studien ergab kein signifikantes Risiko für einen dieser Faktoren. Bezüglich PPARG C161T hatten die Träger der T Variante des C161T Polymorphismus ein erhöhtes Risiko, eine CHD zu bekommen (OR = 1.182, 95 % CI: 1.023–1.341, Pheterogeneity = 0.002). In der stratifizierten Analyse auf ethnische Unterschiede und Ursprung der Kontrollen ergab der Kontrast von CT + TT versus CC bei asiatischen und aus dem Spital ausgesuchten Kontrollen, eine signifikante Assoziation (OR = 1.276, 95 % CI: 1.084–1.468, Pheterogeneity = 0.055; OR = 1.164, 95 % CI: 1.001–1.326, Pheterogeneity = 0.00). Diese Signifikanz ergab sich allerdings nur bei Berechnung mittels des fixed-effect Modells. Die Berechnung mit Hilfe des Random-Effect Modells ergab keine Signifikanz.

Schlussfolgerung

Entsprechend den Ergebnissen dieser Metaanalyse scheint der PPARGC161T Polymorphismus nur marginal zu einer erhöhten Anfälligkeit, eine CHD zu bekommen, beizutragen. Die gering erhöhte Assoziation zwischen dem PPARGH477H Polymorphismus und der CHD war auch bei Asiaten und bei aus dem Spital rekrutierten Kontrollen zu beobachten. Der PPARGP12A Polymorphismus ist allerdings nicht mit einem erhöhten Risiko, an einer CHD zu leiden, assoziiert.

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Conflict of interest

The authors declare that there is no actual or potential conflict of interest in relation to this article.

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Authors and Affiliations

  1. Department of Surgery Laboratory, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000, Zhejiang, P.R. China

    Saidan Ding, Leping Liu, Xing Zhang, Jieya Xie, Weilong Hong, Silu Wang, Yunxiu Yang & Bicheng Chen MD

  2. Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, 325000, Zhejiang, P.R. China

    Zhen Yu

  3. Neurosurgery Department, The First Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, P.R. China

    Qǐ-Chuan Zhuge

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  1. Saidan Ding
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Correspondence to Bicheng Chen MD.

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Ding, S., Liu, L., Zhuge, QC. et al. The meta-analysis of the association of PPARG P12A, C161T polymorphism and coronary heart disease. Wien Klin Wochenschr 124, 671–677 (2012). https://doi.org/10.1007/s00508-012-0223-0

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  • DOI: https://doi.org/10.1007/s00508-012-0223-0

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