Host Single Nucleotide Polymorphisms of MMP‐9 −1562/TIMP‐1 372 Have Gender Differences in the Risk of Gastric Intestinal Metaplasia After Helicobacter pylori Infection

Hung, Kuo Hsiang; Hung, H W; Yang, Hsiao Bai; Lu, Chuanyong; Wu, Jiunn Jong; Sheu, Bor Shyang

doi:10.1111/j.1523-5378.2009.00717.x

Cited by 17 publications

(20 citation statements)

References 34 publications

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“…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%

“…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: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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 higher level of TIMP-1 expression is seen in gastric ulcers where it was suggested as a distinctive marker for discriminating H. pylori and NSAID related ulcers [105,106]. All TIMPs were found to be deregulated in gastric cancer [54,71,83] and polymorphisms in the loci of TIMP-1 and TIMP-2 have been associated with intestinal metaplasia or poor prognosis, respectively [107,108]. The prominent role of TIMP-3 in regulating proteolysis in vivo is highlighted by the observation, that expression levels of TIMP-3 decline while MMP-3 levels increasing during progression of gastric cancer [83] (Table 2, Figure 1).…”

Section: Deregulation Of Extracellular Host Proteases By H Pylorimentioning

confidence: 99%

Proteolysis in Helicobacter pylori-Induced Gastric Cancer

Posselt

Crabtree

Weßler

2017

Toxins

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Persistent infections with the human pathogen and class-I carcinogen Helicobacter pylori (H. pylori) are closely associated with the development of acute and chronic gastritis, ulceration, gastric adenocarcinoma and lymphoma of the mucosa-associated lymphoid tissue (MALT) system. Disruption and depolarization of the epithelium is a hallmark of H. pylori-associated disorders and requires extensive modulation of epithelial cell surface structures. Hence, the complex network of controlled proteolysis which facilitates tissue homeostasis in healthy individuals is deregulated and crucially contributes to the induction and progression of gastric cancer through processing of extracellular matrix (ECM) proteins, cell surface receptors, membrane-bound cytokines, and lateral adhesion molecules. Here, we summarize the recent reports on mechanisms how H. pylori utilizes a variety of extracellular proteases, involving the proteases Hp0169 and high temperature requirement A (HtrA) of bacterial origin, and host matrix-metalloproteinases (MMPs), a disintegrin and metalloproteinases (ADAMs) and tissue inhibitors of metalloproteinases (TIMPs). H. pylori-regulated proteases represent predictive biomarkers and attractive targets for therapeutic interventions in gastric cancer.

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“…In addition, WNT signaling pathway gene polymorphisms are related to the risk of hepatic fibrosis and inflammation in HCV-infected patients (141). In Helicobacter pylori infection, SNPs of MMP-9 -1562/ TIMP-1 372 have been associated with an enhanced risk of gastric intestinal metaplasia (142). With regard to TB there are indications that certain SNPs are associated - not just with the consequences of the disease as described above but with disease susceptibility (143).…”

Section: Wnts and The Susceptibility To Infectious Diseasementioning

confidence: 99%

The Wnt Blows: On the Functional Role of Wnt Signaling in Mycobacterium tuberculosis Infection and Beyond

Brandenburg

Reiling

2016

Front. Immunol.

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In recent years, it has become apparent that the Wnt signaling pathway, known for its essential functions in embryonic development and tissue homeostasis, exerts immunomodulatory functions during inflammation and infection. Most functional studies indicate that Wnt5a exerts pro-inflammatory functions on its cellular targets, which include various types of immune and non-immune cells. Wnt5a expression has also been linked to the pathogenesis of chronic inflammatory diseases. Activation of beta-catenin-dependent Wnt signaling, e.g., by Wnt3a, has however been shown to limit inflammation by interfering with the nuclear factor kappa-light chain-enhancer of activated B-cells (NF-kappaB) pathway. This review focuses on the regulation of Wnt5a, Wnt3a, and the recently identified Wnt6 and their functional role in bacterial infections with a primary focus on pulmonary tuberculosis, a leading infectious cause of morbidity and mortality worldwide.

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Host Single Nucleotide Polymorphisms of MMP‐9 −1562/TIMP‐1 372 Have Gender Differences in the Risk of Gastric Intestinal Metaplasia After Helicobacter pylori Infection

Abstract: The host MMP-9 -1562/TIMP-1 372 SNPs had gender differences in the risk of IM after H. pylori infection, and could possibly serve as a host factor to identify the risk group harboring gastric precancerous changes after H. pylori infection.

Cited by 17 publications

References 34 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

Proteolysis in Helicobacter pylori-Induced Gastric Cancer

The Wnt Blows: On the Functional Role of Wnt Signaling in Mycobacterium tuberculosis Infection and Beyond

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