Nucleotide-Binding Oligomerization Domain-Containing Protein 2 Variants in Patients with Spontaneous Bacterial Peritonitis

Harputluoğlu, Murat; Dertli, Ramazan; Otlu, Barış; Demirel, Ulvi; Yener, O; Bilgiç, Yılmaz; Erdoğan, Mehmet Ali; Atayan, Yahya; Çağın, Yasir Furkan

doi:10.1007/s10620-015-4024-y

Cited by 11 publications

(14 citation statements)

References 35 publications

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“…However, NOD2‐G908, MBL_Yx and MASP2_371 genetic variants were associated with a significantly higher short‐term mortality in patients with an acute bacterial infection. The NOD2‐G908 gene variant has previously been shown to be associated with increased translocation of bacterial DNA fragments in ascitic fluid in patients with culture‐positive SBP . These studies support the functional relevance of this single nucleotide polymorphism.…”

Section: Discussionsupporting

confidence: 62%

“…Bacterial translocation and activation of the innate immune response play important roles in the development of AD in patients with cirrhosis . Innate pattern recognition receptors such as NOD2 receptors are involved in the recognition and clearance of bacterial pathogens and the presence of genetic alterations in these receptors may cause impaired immune function and increased bacterial translocation . The association between NOD2 genetic variants and bacterial infection and mortality have been subject of previous studies, showing conflicting results.…”

Section: Discussionmentioning

confidence: 99%

“…In this study we assessed the association between single nucleotide polymorphisms (SNPs) in the lectin complement pathway and innate immune signalling components for pathogen recognition and the occur- translocation. 23,24 The association between NOD2 genetic variants Note: In univariate analysis only SNPs with P-value < .2 are presented, which were included in the multivariate analysis. In the multivariate logistic regression model CLIF-C score, WBC and prophylactic use of AB were taken as independent variables.…”

Section: Discussionmentioning

confidence: 99%

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Genetic variants of innate immunity receptors are associated with mortality in cirrhotic patients with bacterial infection

Schaapman

Amorós

Reijden

et al. 2020

Liver International

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Background & Aims Acute‐on‐chronic liver failure (ACLF) is characterized by acute decompensation of cirrhosis (AD), organ failure(s) and high risk of short‐term mortality with bacterial infection frequently as precipitating event. Innate immune pattern recognition receptors and members of the lectin pathway of complement activation are crucial to the innate immune response to pathogens. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) of innate immune components are associated with the occurrence of bacterial infections or mortality in patients with cirrhosis hospitalized for AD or ACLF. Methods Twenty‐one innate immunity SNPs with known functional implications were genotyped in 826 AD/ACLF patients included in the CANONIC study. Associations between baseline characteristics of the patients, the occurrence of bacterial infections and survival rate at 90 days of follow‐up in relation to the innate immunity genetic variants were analysed. Results The NOD2‐G908R genetic variant was associated with mortality (HR 2.25, P = .004) independently of age and MELD Score. This association was also found in a predefined subgroup analysis in patients with bacterial infections (HR 2.78, P < .001) along with MBL_Yx (HR 1.72, P = .008) and MASP2_371 (HR 1.67, P = .012) genetic variants. None of the analysed SNPs were significantly associated with the occurrence of acute bacterial infections or spontaneous bacterial peritonitis in particular. Conclusions Innate immune system‐specific NOD2‐G908R, MBL_Yx and MASP2_371 genetic variants were independently associated with increased risk of short‐term mortality in AD/ACLF patients with bacterial infection.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Genetic variants of innate immunity receptors are associated with mortality in cirrhotic patients with bacterial infection

Schaapman

Amorós

Reijden

et al. 2020

Liver International

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“…There is evidence that variants of the NOD2 gene, and various TLR polymorphisms contribute to BT in patients with Crohn's diseases. Likewise in patients with decompensated cirrhosis an increased translocation of bacterial DNA fragments into ascitic fluid was found in the presence of the NOD2 risk variant p.G908R . Moreover, there was increased transition of pathological BT to culture‐positive SBP in the case of the same NOD2 variant .…”

Section: Discussionmentioning

confidence: 94%

Functional polymorphisms of innate immunity receptors are not risk factors for the non‐SBP type bacterial infections in cirrhosis

Dinya

Tornai

Vitális

et al. 2018

Liver International

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“…First, in the light of increasing antimicrobial resistance, individualized approaches that direct antimicrobial prophylaxis only to patients with the highest risk are warranted. NOD2 genotype-based prophylaxis is currently investigated as a rationale for primary prophylaxis for SBP 31 but could not be replicated consistently as it may be stronger associated with culture-positive variants of peritonitis 8, 11, 32 . The risk of SBP was the highest in NOD2 wild type patients with the TRAF6 risk haplotype 2, extending the population at risk for genotype-based primary interventions.…”

Section: Discussionmentioning

confidence: 99%

Genetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study

Mai

Stengel

Al-Herwi

et al. 2017

Sci Rep

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Alterations of the innate immunity contribute to the development of spontaneous bacterial peritonitis (SBP) in liver cirrhosis. Given its role in immune signaling, antimicrobial function, and macrophage differentiation, we hypothesized that genetic polymorphisms of TRAF6 modulate the risk of SBP. Thus, we determined theTRAF6 haplotype in 432 patients with cirrhosis and ascites using the haplotype-tagging single nucleotide polymorphisms rs331457 and rs5030419. In addition, peritoneal macrophages were immunomagnetically isolated and characterized. Overall, 122 (28%) patients had an episode of SBP. In the combined prospective-retrospective analysis the frequency of SBP differed between the four haplotypes (P = 0.014) and was the highest in 102 patients carrying the rs331457 but not the rs5030419 variant, when compared to other haplotypes (odds ratio 1.95 [1.22–3.12]) or to the wild-type (odds ratio 1.71 [1.04–2.82]). This association was confirmed in multivariate logistic regression (adjusted odds ratio 2.00 [1.24–3.22]) and in prospective sensitivity analysis (hazard ratio 2.09 [1.08–4.07]; P = 0.03). The risk haplotype was associated with lower concentrations of the immune activation marker soluble CD87 in ascitic fluid and with a decreased expression of IL-6 and CXCL8 in isolated peritoneal macrophages. In conclusion, genetic polymorphisms of TRAF6 are associated with decreased peritoneal immune activation and an increased risk of SBP.

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Nucleotide-Binding Oligomerization Domain-Containing Protein 2 Variants in Patients with Spontaneous Bacterial Peritonitis

Cited by 11 publications

References 35 publications

Genetic variants of innate immunity receptors are associated with mortality in cirrhotic patients with bacterial infection

Genetic variants of innate immunity receptors are associated with mortality in cirrhotic patients with bacterial infection

Functional polymorphisms of innate immunity receptors are not risk factors for the non‐SBP type bacterial infections in cirrhosis

Genetic variants of TRAF6 modulate peritoneal immunity and the risk of spontaneous bacterial peritonitis in cirrhosis: A combined prospective-retrospective study

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