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Genetic and biochemical heterogeneity of cardiac troponins: clinical and laboratory implications

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Published/Copyright: September 16, 2009
Clinical Chemistry and Laboratory Medicine
From the journal Clinical Chemistry and Laboratory Medicine Volume 47 Issue 10

Abstract

The contractile sarcomeric pool of skeletal muscle and heart consists of a highly-ordered arrangement of actin thin filaments, tropomyosin and proteins of the troponin complex: troponin I (TnI), troponin T (TnT) and troponin C (TnC). The cardiac myocyte expresses specific isoforms of both TnI and TnT (cTnI and cTnT, respectively), which can be distinguished from skeletal muscle isoforms by rapid and reliable immunoassays. Due to their superior cardiac specificity, cTnI and cTnT have become the recommended biomarkers for the diagnosis of myocardial injury. The most common applications are for risk stratification and diagnosis of acute coronary syndromes, albeit they can also be used for assessing a variety of other myocardial disorders. However, the excellent diagnostic efficiency of cardiac troponin testing is jeopardized by some pre-analytical issues (unsuitable specimens for testing, analyte stability, handling, transportation and storage of specimens prior to analysis), as well as by analytical concerns related to standardization or harmonization of cTnI immunoassays, imprecision at low concentrations, antibody specificity, immunoreactivity of plasma isoforms released in the blood after myocardial injury, interference from autoantibodies, heterophilic antibodies, rheumatoid factor, and human anti-mouse antibodies. In addition, although the influence of some known mutations in cTnT and cTnI on calcium sensitivity and force generation have been readily demonstrated, their influence on current immunoassays is unknown. Most mutations in these proteins may contribute to the development of certain cardiomyopathies, namely hypertrophic and restrictive. In these situations, the phenotype is characterized by the underlying diseases, and the ability to detect cTnT or cTnI is of relatively little clinical significance. However, the cTnT Arg129Lys polymorphism and those observed in the stable domain of cTnI do not significantly alter the functional properties of the molecule within the myocardium and thus are predictably asymptomatic. While the actual prevalence of these polymorphisms in the general population is still unknown, they might be a source of potential analytical problems; modifying the immunogenicity of the molecule and leading to potential false negative results. The goal of this article is to provide an overview on the potential technical and analytical challenges in the measurement of cardiac troponins, along with the significance of polymorphisms in the genes encoding for cTnI and cTnT in both health and disease.

Clin Chem Lab Med 2009;47:1183–94.

Keywords: cardiac markers; genetics; myocardial infarction; troponin
Corresponding author: Prof. Giuseppe Lippi, MD, Sezione di Chimica e Microscopia Clinica, Dipartimento di Scienze Morfologico-Biomediche, Università degli Studi di Verona, Ospedale Policlinico G.B. Rossi, Piazzale Scuro, 10, 37134 Verona, Italy Phone: +39-045-8124308, Fax: +39-045-8027484, ,
Received: 2009-8-6
Accepted: 2009-8-11
Published Online: 2009-09-16
Published in Print: 2009-10-01

©2009 by Walter de Gruyter Berlin New York

Articles in the same Issue

  1. Editorial
  2. Cardiac troponins: what we knew, what we know – where are we now?
  3. Review
  4. Measurement of circulating concentrations of cardiac troponin I and T in healthy subjects: a tool for monitoring myocardial tissue renewal?
  5. Opinion Papers
  6. A critical appraisal of experimental factors influencing the definition of the 99th percentile limit for cardiac troponins
  7. Genetic and biochemical heterogeneity of cardiac troponins: clinical and laboratory implications
  8. The future of hospital laboratories. Position statement from the Royal Belgian Society of Clinical Chemistry (RBSCC)
  9. Point
  10. Quantity quotient reporting. A proposal for a standardized presentation of laboratory results
  11. Counterpoint
  12. Quantity quotient reporting. Counterpoint
  13. Perspectives
  14. Increasing laboratory medicine activities in China: research and publications
  15. Contributions in Biochemistry and Molecular Biology from China and other top-ranking countries: a 10-year survey of the literature
  16. Genetics and Molecular Diagnostics
  17. SOCS3 and IRS-1 gene expression differs between genotype 1 and genotype 2 hepatitis C virus-infected HepG2 cells
  18. Polymorphisms of the β1-adrenergic receptor gene are associated with essential hypertension in Chinese
  19. Egyptian glycogen storage disease type III – identification of six novel AGL mutations, including a large 1.5 kb deletion and a missense mutation p.L620P with subtype IIId
  20. Novel rare alleles of ABCA1 are exclusively associated with extreme high-density lipoprotein-cholesterol levels among the Han Chinese
  21. –308G>A and –1031T>C tumor necrosis factor gene polymorphisms in Tunisian patients with coronary artery disease
  22. General Clinical Chemistry and Laboratory Medicine
  23. Error tracking in a clinical biochemistry laboratory
  24. HbA1c measurements from dried blood spots: validation and patient satisfaction
  25. Pre-transplant serum concentrations of anti-endothelial cell antibody in panel reactive antibody negative renal recipients and its impact on acute rejection
  26. Cancer Diagnostics
  27. Detection of Meningeosis neoplastica by real-time quantitation of telomerase activity
  28. The prognostic utility of haptoglobin genotypes in squamous cell carcinoma of the head and neck
  29. Evaluation of a new method for the diagnosis of alterations of Lens culinaris agglutinin binding of thyroglobulin molecules in thyroid carcinoma
  30. The soluble transferrin receptor (TfR)-F-Index is not applicable as a test for iron status in patients with chronic lymphocytic leukemia
  31. Impact of calibration fitting models on the clinical value of chromogranin A
  32. Letters to the Editor
  33. Clinical value of a competitive NT-proBNP enzyme immunoassay compared to the Roche NT-proBNP platform
  34. Should gender-related reference values be used for total bilirubin?
  35. A novel nonsense mutation in the albumin gene (c.1275 C>A) causing analbuminemia in a Tunisian boy
  36. Abstracts
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https://doi.org/10.1515/CCLM.2009.322
Keywords for this article
cardiac markers; genetics; myocardial infarction; troponin

Articles in the same Issue

  1. Editorial
  2. Cardiac troponins: what we knew, what we know – where are we now?
  3. Review
  4. Measurement of circulating concentrations of cardiac troponin I and T in healthy subjects: a tool for monitoring myocardial tissue renewal?
  5. Opinion Papers
  6. A critical appraisal of experimental factors influencing the definition of the 99th percentile limit for cardiac troponins
  7. Genetic and biochemical heterogeneity of cardiac troponins: clinical and laboratory implications
  8. The future of hospital laboratories. Position statement from the Royal Belgian Society of Clinical Chemistry (RBSCC)
  9. Point
  10. Quantity quotient reporting. A proposal for a standardized presentation of laboratory results
  11. Counterpoint
  12. Quantity quotient reporting. Counterpoint
  13. Perspectives
  14. Increasing laboratory medicine activities in China: research and publications
  15. Contributions in Biochemistry and Molecular Biology from China and other top-ranking countries: a 10-year survey of the literature
  16. Genetics and Molecular Diagnostics
  17. SOCS3 and IRS-1 gene expression differs between genotype 1 and genotype 2 hepatitis C virus-infected HepG2 cells
  18. Polymorphisms of the β1-adrenergic receptor gene are associated with essential hypertension in Chinese
  19. Egyptian glycogen storage disease type III – identification of six novel AGL mutations, including a large 1.5 kb deletion and a missense mutation p.L620P with subtype IIId
  20. Novel rare alleles of ABCA1 are exclusively associated with extreme high-density lipoprotein-cholesterol levels among the Han Chinese
  21. –308G>A and –1031T>C tumor necrosis factor gene polymorphisms in Tunisian patients with coronary artery disease
  22. General Clinical Chemistry and Laboratory Medicine
  23. Error tracking in a clinical biochemistry laboratory
  24. HbA1c measurements from dried blood spots: validation and patient satisfaction
  25. Pre-transplant serum concentrations of anti-endothelial cell antibody in panel reactive antibody negative renal recipients and its impact on acute rejection
  26. Cancer Diagnostics
  27. Detection of Meningeosis neoplastica by real-time quantitation of telomerase activity
  28. The prognostic utility of haptoglobin genotypes in squamous cell carcinoma of the head and neck
  29. Evaluation of a new method for the diagnosis of alterations of Lens culinaris agglutinin binding of thyroglobulin molecules in thyroid carcinoma
  30. The soluble transferrin receptor (TfR)-F-Index is not applicable as a test for iron status in patients with chronic lymphocytic leukemia
  31. Impact of calibration fitting models on the clinical value of chromogranin A
  32. Letters to the Editor
  33. Clinical value of a competitive NT-proBNP enzyme immunoassay compared to the Roche NT-proBNP platform
  34. Should gender-related reference values be used for total bilirubin?
  35. A novel nonsense mutation in the albumin gene (c.1275 C>A) causing analbuminemia in a Tunisian boy
  36. Abstracts
  37. 41st National Congress of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology, 2nd Joint National Event SIBioC-SIMeL
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