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Licensed Unlicensed Requires Authentication Published by De Gruyter April 9, 2014

Interleukin-6 receptor Asp358Ala gene polymorphism is associated with plasma C-reactive protein levels and severity of aortic valve stenosis

  • Ewa Wypasek EMAIL logo , Daniel P. Potaczek , Markus Lamplmayr , Jerzy Sadowski and Anetta Undas


Background: Interleukin-6 receptor (IL-6R) gene Asp358Ala (A>C, rs2228145) polymorphism has been associated with lower circulating inflammation biomarkers in coronary artery disease (CAD), such as C-reactive protein (CRP) or fibrinogen, but its role in the pathogenesis of aortic valve stenosis (AS) remains unknown. Since the pathogenesis of AS and atherosclerosis shares several similarities, we tested the hypothesis that IL-6R Asp358Ala polymorphism is associated with the severity of AS.

Methods: A total of 284 AS patients aged 64.3±11.1 years were studied, in whom IL-6R polymorphism was determined by TaqMan genotyping.

Results: The genotype distribution was as follows: AA-43.7% (n=124); AC-37.0% (n=105); and CC-19.4% (n=55). For every copy of C allele inherited, mean concentration of CRP was reduced by 22% (95% CI 13.8–30.4; p<0.0001). Carriers of the C allele compared to the AA homozygotes were also characterized by lower mean and maximal transvalvular gradients [44.8 (30.5–60.0) vs. 52.7 (40.5–69.0) mmHg, p=0.0005; and 78.1±26.5 vs. 87.3±27.6 mmHg; p=0.008, respectively], and larger aortic valve area [0.8 (0.6–1.0) vs. 0.7 (0.5–0.9) cm2, p=0.005].

Conclusions: Our study is the first to show that the presence of the IL-6R 358Ala allele in AS patients is associated with attenuated systemic inflammatory state and less severe AS.

Corresponding author: Ewa Wypasek, Institute of Cardiology, Jagiellonian University School of Medicine, 80 Pradnicka Street, 31-202 Cracow, Poland; and John Paul II Hospital, Cracow, Poland, Phone: +48 12 6143145, Fax: +48 12 6143145, E-mail:
aEwa Wypasek and Daniel P. Potaczek contributed equally to this work.


The study has been supported by a grant of the Polish Ministry of Science (K/ZDS/002936 to A.U.).

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research support played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.


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Received: 2013-7-30
Accepted: 2014-3-13
Published Online: 2014-4-9
Published in Print: 2014-7-1

©2014 by Walter de Gruyter Berlin/Boston

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