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dc.creatorLorente, L. (Leonardo)-
dc.creatorMartin, M. (Mar)-
dc.creatorPlasencia, F. (Fátima)-
dc.creatorSole-Violan, J. (Jordi)-
dc.creatorBlanquer, J. (José)-
dc.creatorLabarta, L. (Lorenzo)-
dc.creatorDíaz, C. (César)-
dc.creatorBorreguero-Leon, J.M. (Juan María)-
dc.creatorJimenez, A. (Alejandro)-
dc.creatorParamo, J.A. (José Antonio)-
dc.creatorOrbe, J. (Josune)-
dc.creatorRodriguez, J.A. (José Antonio)-
dc.creatorSalido, E. (Eduardo)-
dc.date.accessioned2019-06-11T07:32:17Z-
dc.date.available2019-06-11T07:32:17Z-
dc.date.issued2013-
dc.identifier.citationLorente, L. (Leonardo); Martin, M. (Mar); Plasencia, F. (Fátima); et al. "The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis". Critical care. 17, 2013, 1 - 8es_ES
dc.identifier.issn1364-8535-
dc.identifier.urihttps://hdl.handle.net/10171/57771-
dc.description.abstractIntroduction: Previous studies have found higher circulating levels of tissue inhibitor of matrix metalloproteinase (TIMP)-1 in nonsurviving septic patients than in surviving septic patients, and an association between the 372 T/C genetic polymorphism of TIMP-1 and the risk of developing certain diseases. However, the relationship between genetic polymorphisms of TIMP-1, circulating TIMP-1 levels and survival in patients with severe sepsis has not been examined, and this was the objective of the study. Methods: This multicentre, prospective, observational study was carried out in six Spanish ICUs. We determined the 372 T/C genetic polymorphism of TIMP-1 (rs4898), serum levels of TIMP-1, matrix metalloproteinase (MMP)-9, MMP-10, TNFa, IL-10 and plasma plasminogen activator inhibitor-1 (PAI-1). Survival at 30 days from ICU admission was the endpoint assessed. The association between continuous variables was carried out using Spearman’s rank correlation coefficient or Spearman’s rho coefficient. Multivariate logistic regression analysis was applied to determine the association between the 372 T/C genetic polymorphism and survival 30 days from ICU admission. Results: Of 275 patients with severe sepsis, 80 had genotype CC, 55 had genotype CT and 140 had genotype TT of the 372 T/C genetic polymorphism of TIMP-1. Patients with the T allele showed higher serum levels of TIMP-1 than patients without the T allele (P = 0.004). Multiple logistic regression analysis showed that the T allele was associated with higher mortality at 30 days (odds ratio = 2.08; 95% confidence interval = 1.06 to 4.09; P = 0.03). Survival analysis showed that patients with the T allele presented lower 30-day survival than patients without the T allele (c2 = 5.77; P = 0.016). We found an association between TIMP-1 levels and levels of MMP-9 (r = -0.19; P = 0.002), MMP-10 (r = 0.55; P <0.001), TNFa (r = 0.56; P <0.001), IL-10 (r = 0.48; P <0.001) and PAI-1 (r = 0.49; P <0.001). Conclusion: The novel findings of our study are that septic patients with the T allele in the 372 T/C genetic polymorphism of TIMP-1 showed higher serum TIMP-1 levels and lower survival rate. The determination of the 372 T/C genetic polymorphism of TIMP-1 thus has prognostic implications and could help in the selection of patients who may benefit from modulation of the MMP/TIMP balance.es_ES
dc.description.sponsorshipThis study was supported, in part, by the grants FIS/PI-10-1572, I3SNS-INT-11- 063 and I3SNS-INT-12-087 from Instituto de Salud Carlos III (Madrid, Spain) and by UTE Project CIMA (University of Navarra).es_ES
dc.language.isoenges_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.subjectTissue inhibitor of matrix metalloproteinase-1es_ES
dc.subjectGenerices_ES
dc.subjectPolymorphismes_ES
dc.subjectSepsises_ES
dc.subjectMortalityes_ES
dc.titleThe 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsises_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.description.noteThis is an open access article distributed under the Creative Commons: Atribution License (cc BY)es_ES
dc.identifier.doihttps://doi.org/10.1186/cc12739es_ES
dc.identifier.doi10.1186/cc12739-
dadun.citation.endingPage8es_ES
dadun.citation.publicationNameCritical carees_ES
dadun.citation.startingPage1es_ES
dadun.citation.volume17es_ES

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