%0 Journal Article
%T Key genes of the interleukin 6 signaling pathway are not associated with coronary artery disease in a large European population
%A Mark Luedde
%A Arne S. Schaefer
%A Natalie Scheller
%A Corinna Doege
%A Hans-Joerg Hippe
%A Michael Nothnagel
%A Nils Haake
%A Norbert Frey
%A Stefan Schreiber
%A Nour Eddine El-Mokhtari
%J Open Journal of Genetics
%P 67-78
%@ 2162-4461
%D 2013
%I Scientific Research Publishing
%R 10.4236/ojgen.2013.31008
%X <p style=\"text-align:justify;\">
	<span style=\"font-size:10pt;\"><span style=\"font-size:12px;\">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 </span><i><span style=\"font-size:12px;\">IL</span></i><span style=\"font-size:12px;\">-6 signaling pathway. Results were adjusted to the CAD-related risk factors diabetes, hypertension, Body Mass Index, smoking and sex by logistic regres</span><span style=\"font-size:12px;\">sion analysis. In a primary explorative study, we iden</span><span style=\"font-size:12px;\">tified 5 SNPs that were significantly associated with CAD (</span><i><span style=\"font-size:12px;\">MAPK</span></i><span style=\"font-size:12px;\">1_rs6928, </span><i><span style=\"font-size:12px;\">MAPK</span></i><span style=\"font-size:12px;\">1_rs9340, </span><i><span style=\"font-size:12px;\">MAPK</span></i><span style=\"font-size:12px;\">1_ rs11913721, </span><i><span style=\"font-size:12px;\">MAPK</span></i><span style=\"font-size:12px;\">14_rs7757672, </span><i><span style=\"font-size:12px;\">JAK</span></i><span style=\"font-size:12px;\">1_rs310236). After adjustment to CAD-risk factors, </span><i><span style=\"font-size:12px;\">MAPK</span></i><span style=\"font-size:12px;\">1_ 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 </span><i><span style=\"font-size:12px;\">IL</span></i><span style=\"font-size:12px;\">-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.</span></span> 
</p>
%K Coronary Artery Disease
%K Genetics
%K Single Nucleotide Polymorphism
%K Interleukin 6
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=29373