Author(s)

Mark Luedde, Arne S. Schaefer, Natalie Scheller, Corinna Doege, Hans-Joerg Hippe, Michael Nothnagel, Nils Haake, Norbert Frey, Stefan Schreiber, Nour Eddine El-Mokhtari

Department of Cardiovascular Surgery, University of Kiel, Kiel, Germany.
Department of Internal Medicine III: Cardiology and Angiology, University of Kiel, Kiel, Germany.
Department of Medicine, Christian-Albrechts-Universit?t Kiel, Kiel, Germany.
Department of Pediatric Neurology, University of Kiel, Kiel, Germany.
Imland Klinikum Rendsburg, Christian-Albrechts-Universit?t Kiel, Rendsburg, Germany.
Institute for Clinical Molecular Biology, University of Kiel, Kiel, Germany.
Institute of Medical Informatics and Statistics, University of Kiel, Kiel, Germany.

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.

Coronary Artery Disease; Genetics; Single Nucleotide Polymorphism; Interleukin 6

Luedde, M. , Schaefer, A. , Scheller, N. , Doege, C. , Hippe, H. , Nothnagel, M. , Haake, N. , Frey, N. , Schreiber, S. and El-Mokhtari, N. (2013) Key genes of the interleukin 6 signaling pathway are not associated with coronary artery disease in a large European population. Open Journal of Genetics, 3, 67-78. doi: 10.4236/ojgen.2013.31008.