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The 372 T/C genetic polymorphism of TIMP-1 as a biomarker of mortality in patients with sepsis

Critical Care201317:456

https://doi.org/10.1186/cc13037

  • Published:

Keywords

  • Myocardial Infarction
  • Plasminogen
  • Plasminogen Activator
  • Genetic Polymorphism
  • Septic Patient

In the previous issue of Critical Care, Behnes and colleagues [1] provide an interesting commentary on our study showing that septic patients with the T-allele in 372 T/C (rs4898) genetic polymorphism of the tissue inhibitor of metalloproteinase-1 (TIMP-1) had higher mortality and higher TIMP-1 serum levels than those without it [2].

As the authors state in their commentary, our study had some limitations. One limitation was the relatively small sample size to establish prognostic implications by only one single-nucleotide polymorphism (SNP) challenge. However, the sample size was large enough to find an association between polymorphism and survival.

Another limitation was that we tested only the rs4898 SNP, a tag SNP, for the region of interest. However, it may be that this SNP, which is in strong linkage disequilibrium with other TIMP-1 polymorphisms, is linked to other SNPs associated with the same effect.

Another possibility is that this association represents only an epiphenomenon since, in our study, a cause-effect relationship between polymorphism and mortality was not established. However, we found that patients with the T-allele had higher TIMP-1 serum levels and that patients with higher TIMP-1 circulating levels showed higher mortality [3, 4]. Besides, we found a positive association between TIMP-1 and plasminogen activator inhibitor-1 circulating levels, previously found in myocardial infarction patients [5], probably suggesting a prothrombotic state. In conclusion, we think that the determinations of 372 T/C genetic polymorphism and circulating levels of TIMP-1 could be used as mortality biomarkers in patients with sepsis.

Abbreviations

SNP: 

Single-nucleotide polymorphism

TIMP: 

Tissue inhibitor of matrix metalloproteinase.

Declarations

Acknowledgments

This study was supported, in part, by grants (FIS/PI-10-1572, I3SNS-INT-11-063, and I3SNS-INT-12-087) from Instituto de Salud Carlos III (Madrid, Spain).

Authors’ Affiliations

(1)
Intensive Care Unit, Hospital Universitario de Canarias, Ofra s/n La Laguna, Santa Cruz de Tenerife, 38320, Spain
(2)
Intensive Care Unit, Hospital Universitario Nuestra Señora Candelaria, Carretera Rosario s/n, Santa Cruz de Tenerife, 38010, Spain

References

  1. Behnes M, Bertsch T, Hoffmann : TIMP-1 gene polymorphism: are genetics able to predict outcome of septic patients? Crit Care 2013, 17: 170. 10.1186/cc12799PubMed CentralView ArticlePubMedGoogle Scholar
  2. Lorente L, Martín MM, Plasencia F, Solé-Violán J, Blanquer J, Labarta L, Díaz C, Borreguero-León JM, Jiménez A, Páramo JA, Orbe J, Rodríguez JA, Salido E: The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis. Crit Care 2013, 17: R94. 10.1186/cc12739PubMed CentralView ArticlePubMedGoogle Scholar
  3. Hoffmann U, Bertsch T, Dvortsak E, Liebetrau C, Lang S, Liebe V, Huhle G, Borggrefe M, Brueckmann M: Matrix-metalloproteinases and their inhibitors are elevated in severe sepsis: prognostic value of TIMP-1 in severe sepsis. Scand J Infect Dis 2006, 38: 867-872. 10.1080/00365540600702058View ArticlePubMedGoogle Scholar
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  5. Cavusoglu E, Ruwende C, Chopra V, Yanamadala S, Eng C, Clark LT, Pinsky DJ, Marmur JD: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an independent predictor of all-cause mortality, cardiac mortality, and myocardial infarction. Am Heart J 2006, 151: 1101. e1-8View ArticlePubMedGoogle Scholar

Copyright

© BioMed Central Ltd. 2013

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