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

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Published/Copyright: April 9, 2014
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 52 Issue 7

Abstract

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.

Keywords: aortic stenosis; Asp358Ala IL-6R polymorphism; C-reactive protein (CRP); transvalvular gradient
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.

Acknowledgments

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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https://doi.org/10.1515/cclm-2013-0606
Keywords for this article
aortic stenosis; Asp358Ala IL-6R polymorphism; C-reactive protein (CRP); transvalvular gradient

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Diagnosis of diabetes mellitus: reiterated responsibilities for the clinical laboratory
  4. Review
  5. The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a Mendelian randomization meta-analysis
  6. Opinion Papers
  7. Harmonization of quality indicators in laboratory medicine. A preliminary consensus
  8. Cardiac biomarkers and risk assessment in patients undergoing major non-cardiac surgery: time to revise the guidelines?
  9. General Clinical Chemistry and Laboratory Medicine
  10. A statistical basis for harmonization of thyroid stimulating hormone immunoassays using a robust factor analysis model
  11. Sigma metrics used to assess analytical quality of clinical chemistry assays: importance of the allowable total error (TEa) target
  12. Combined light chain immunofixation to detect monoclonal gammopathy: a comparison to standard electrophoresis in serum and urine
  13. Automated indirect immunofluorescence microscopy enables the implementation of a quantitative internal quality control system for anti-nuclear antibody (ANA) analysis
  14. Peripheral blood lymphocytes from patients with bipolar disorder demonstrate apoptosis and differential regulation of advanced glycation end products and S100B
  15. Coefficient of energy balance, a new parameter for basic investigation of the cerebrospinal fluid
  16. Interconversion of stone composition profiles from two recurrent stone episodes in stone formers
  17. Reference Values
  18. Complete blood count reference intervals and age- and sex-related trends of North China Han population
  19. Cancer Diagnostics
  20. The quantification of HER2 and MYC gene fragments in cell-free plasma as putative biomarkers for gastric cancer diagnosis
  21. Cardiovascular Diseases
  22. Novel sensitive cardiac troponin I immunoassay free from troponin I-specific autoantibody interference
  23. Interleukin-6 receptor Asp358Ala gene polymorphism is associated with plasma C-reactive protein levels and severity of aortic valve stenosis
  24. Diabetes
  25. Stability of glucose in plasma with different anticoagulants
  26. Plasma glucose measurement in diabetes: impact and implications of variations in sample collection procedures with a focus on the first hour after sample collection
  27. Changing from glucose to HbA1c for diabetes diagnosis: predictive values of one test and importance of analytical bias and imprecision
  28. System accuracy evaluation of systems for point-of-care testing of blood glucose: a comparison of a patient-use system with six professional-use systems
  29. Letter to the Editors
  30. Reply to the article entitled “Identification of an 18 bp deletion in the TWIST1 gene by CO-amplification at lower denaturation temperature-PCR (COLD-PCR) for non-invasive prenatal diagnosis of craniosynostosis: first case report” by Galbiati et al., Clin Chem Lab Med 2014;52(4):505–9
  31. Further considerations concerning non-invasive prenatal diagnosis of craniosynostosis based on the identification of an 18 bp deletion in the TWIST1 gene by COLD-PCR
  32. Sensible use of laboratory testing requires active laboratory involvement
  33. Digoxin overdose – an accurate method for determining free digoxin concentrations on general chemistry analysers post DigiFab treatment
  34. Method-specific differences in β-isomerised carboxy-terminal cross-linking telopeptide of type I collagen and procollagen type I amino-terminal propeptide using two fully automated immunoassays
  35. Evaluation of mutation profiling by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry in fine needle aspirations from papillary thyroid cancer
  36. Evaluation of Calfast® immunochromatographic quantitative assay for the measurement of calprotectin in faeces
  37. Measurement error in estimated average glucose: a novel approach
  38. Feasibility of an EQAS for HbA1c in Italy using fresh blood samples
  39. Congress Abstracts
  40. 5th Annual International Symposium on Kallikreins and Kallikrein-Related Peptidases
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