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Schunkert, H., Gotz, A., Braund, P., McGinnis, R., Tregouet, D.A., Mangino, M., Linsel-Nitschke, P., Cambien, F., Hengstenberg, C., Stark, K., Blankenberg, S., Tiret, L., Ducimetiere, P., Keniry, A., Ghori, M.J., Schreiber, S., El Mokhtari, N.E., Hall, A.S., Dixon, R.J., Goodall, A.H., Liptau, H., Pollard, H., Schwarz, D.F., Hothorn, L.A., Wichmann, H.E., Konig, I.R., Fischer, M., Meisinger, C., Ouwehand, W., Deloukas, P., Thompson, J.R., Erdmann, J., Ziegler, A. and Samani, N.J. (2008) Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease. Circulation, 117, 1675-1684.
doi:10.1161/CIRCULATIONAHA.107.730614
has been cited by the following article:
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TITLE:
Key genes of the interleukin 6 signaling pathway are not associated with coronary artery disease in a large European population
AUTHORS:
Mark Luedde, Arne S. Schaefer, Natalie Scheller, Corinna Doege, Hans-Joerg Hippe, Michael Nothnagel, Nils Haake, Norbert Frey, Stefan Schreiber, Nour Eddine El-Mokhtari
KEYWORDS:
Coronary Artery Disease; Genetics; Single Nucleotide Polymorphism; Interleukin 6
JOURNAL NAME:
Open Journal of Genetics,
Vol.3 No.1,
March
29,
2013
ABSTRACT:
Background: Recent studies indicate a strong functional relevance of the canonical inflammatory interleukin 6 signaling pathway in coronary artery disease (CAD). A genetic association of this signaling pathway with CAD has not been shown yet. We aimed to assess novel single nucleotide polymorphisms (SNPs) from genes of the Interleukin 6 signaling pathway. Results: To identify novel SNPs that are relevant for CAD, we employed a large-scale population-based case-control association study of 2199 cases and 1715 controls and assessed 73 SNPs from 12 genes out of the IL-6 signaling pathway. Results were adjusted to the CAD-related risk factors diabetes, hypertension, Body Mass Index, smoking and sex by logistic regression analysis. In a primary explorative study, we identified 5 SNPs that were significantly associated with CAD (MAPK1_rs6928, MAPK1_rs9340, MAPK1_ rs11913721, MAPK14_rs7757672, JAK1_rs310236). After adjustment to CAD-risk factors, MAPK1_ rs6928 showed the strongest association with CAD (P 0.0217, Odds Ratio 1.36, Confidence Interval 1.05 - 1.77). To reproduce this result, we performed a replication study employing independent patient and control panels. In this study we could not approve the association of rs6928 with CAD. Conclusion: In conclusion, we did not detect significant associations of SNPs from the IL-6 signaling pathway with CAD. Our investigation demonstrates the importance of independent replication studies to verify results from candidate-gene association studies in the quest to discover the underlying pathomechanism of CAD.
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