Association of TIMP-1 +372 SNP with digital ulcer manifestation in female systemic sclerosis patients

Skarmoutsou, Evangelia; D’Amico, Fabio; Marchini, Maurizio; Malaponte, Grazia; Scorza, Raffaella; Mazzarino, María Clorinda

doi:10.1016/j.humimm.2012.07.040

Cited by 14 publications

(12 citation statements)

References 27 publications

(29 reference statements)

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“…However, an association between the 372 T/C genetic polymorphism of TIMP-1 and survival in patients with severe sepsis has not been previously reported. The results of the different studies are controversial; some found that the C allele was associated with higher risk of certain diseases [10-13] while others showed that the T allele was associated with higher risk [14-16]. In the present study, septic patients with the T allele had a lower rate of survival at 30 days.…”

Section: Discussioncontrasting

confidence: 51%

“…Although the exact mechanism by which this synonymous SNP might affect function is unknown, the 372 T/C genetic polymorphism of TIMP-1 has been associated with increased risk of developing certain diseases [10-16]. However, an association between the 372 T/C genetic polymorphism of TIMP-1 and survival in patients with severe sepsis has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

“…First, the sample size was relatively small; nevertheless, our nonprobabilistic sample was large enough to be able to show an association between the 372 T/C genetic polymorphism of TIMP-1 and 30-day survival. Second, it could be interesting to determine other SNPs of TIMP-1; however, we tested rs4898 because this SNP has previously been associated with other diseases [10-16]. rs4898 is a synonymous coding SNP, but it is in strong linkage disequilibrium with other TIMP-1 polymorphisms, as documented in the HapMap database for European Community populations [26].…”

Section: Discussionmentioning

confidence: 99%

“…An association between some genetic polymorphisms of the X-linked TIMP-1 gene and the risk of developing certain diseases has been reported [10-23], the 372 T/C polymorphism being the variant most studied [10-16]. However, the relationship between genetic polymorphism of TIMP-1, circulating TIMP-1 levels and survival in patients with severe sepsis has not been examined.…”

Section: Introductionmentioning

confidence: 99%

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The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis

et al. 2013

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IntroductionPrevious 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.MethodsThis 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, TNFα, 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.ResultsOf 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 (χ2 = 5.77; P = 0.016). We found an association between TIMP-1 levels and levels of MMP-9 (ρ = -0.19; P = 0.002), MMP-10 (ρ = 0.55; P <0.001), TNFα (ρ = 0.56; P <0.001), IL-10 (ρ = 0.48; P <0.001) and PAI-1 (ρ = 0.49; P <0.001).ConclusionThe 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.

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Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis

et al. 2013

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“…A study by Skarmoutsou and colleagues demonstrated the prognostic impact of the 372 T/C TIMP-1 genetic polymorphism for the onset of systemic sclerosis in women [7]. An association of genetic polymorphisms of the X-linked TIMP-1 gene with the risk of developing certain other diseases has been reported, the 372 T/C TIMP-1 polymorphism being the most studied variant [7-9]. …”

Section: Introductionmentioning

confidence: 99%

TIMP-1 gene polymorphism: are genetics able to predict outcome of septic patients?

2013

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The multicenter study conducted by Lorente and coworkers - published in the previous issue of Critical Care - suggests that levels of tissue inhibitor of metalloproteinase (TIMP)-1 in association with the 372 T/C genetic polymorphism of TIMP-1 are promising markers to predict the clinical outcome of septic patients. TIMPs bind to active matrix metalloproteinases and, amongst other effects, inhibit their proteolytic activity of the extracellular matrix. Previous clinical studies showed increased plasma levels of TIMP-1 in nonsurvivors of sepsis, and showed associations between the 372 T/C genetic polymorphism of TIMP-1 and increased risk of developing certain diseases. In recent years, there has been great interest in understanding whether genetic determinants of the host response to systemic infections are associated with poor outcome. Furthermore, the pharmacogenomics of sepsis may allow us to target immune-modulating therapies. Measurement of TIMP-1 protein levels and TIMP-1 polymorphism 372 T/C in the intensive care setting could therefore be an attractive noninvasive tool to determine the outcome of septic patients, and might help to select patients potentially benefitting from a target-specific immune-modulatory therapy directed to matrix metalloproteinase/TIMP homeostasis.

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The Immunogenetics of Systemic Sclerosis

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Türsen

Rajabi

et al. 2022

The Immunogenetics of Dermatologic Diseases

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Association of TIMP-1 +372 SNP with digital ulcer manifestation in female systemic sclerosis patients

Cited by 14 publications

References 27 publications

The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis

The 372 T/C genetic polymorphism of TIMP-1 is associated with serum levels of TIMP-1 and survival in patients with severe sepsis

TIMP-1 gene polymorphism: are genetics able to predict outcome of septic patients?

The Immunogenetics of Systemic Sclerosis

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