Tumor necrosis factor gene polymorphism and septic shock in surgical infection

Tang, Gau Jun; Huang, Song Lih; Yien, Huey-Wen; Chen, Wei Shone; Wen, Chin; Wu, Chew Wun; Lui, Wing Yiu; Chiu, Jen‐Hwey; Lee, Tak Yu

doi:10.1097/00003246-200008000-00008

Cited by 163 publications

(62 citation statements)

References 20 publications

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“…In particular, we were unable to confirm previous findings of significant associations between the TNF À308 and the LTA þ 249 SNPs and susceptibility to, or outcome from severe sepsis and septic shock. 7-9,24-26 Also, in keeping with one earlier study, 7 we were unable to confirm previous findings of an association between either the TNF À308 SNP 8,25 or the LTA þ 249 SNP 9 and circulating levels of TNF. Such inconsistency has been a common experience with candidate gene association studies in many diseases, 35 and in particular with those which have examined TNF polymorphisms.…”

Section: Discussioncontrasting

confidence: 60%

“…Although several studies have found an association of the A allele with a predisposition to septic shock and/or outcome from sepsis, findings have been inconsistent (Table 1). 7,8,[23][24][25][26] One explanation for these contradictory observations may be the linkage disequilibrium (LD), which is known to exist between this SNP and other functionally important polymorphisms in the region, and it is notable that only one previous study has investigated TNF haplotype associations in patients with sepsis. 26 Moreover, although the A allele of the À308 SNP has been shown to increase TNF transcription in some in vitro studies, 27 in others this has not been the case, 28 leading some to question the functional importance of this SNP.…”

Section: Introductionmentioning

confidence: 99%

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TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study

et al. 2004

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Tumour necrosis factor (TNF) is an important pro-inflammatory cytokine produced in sepsis. Studies examining the association of individual TNF single nucleotide polymorphisms with sepsis have produced conflicting results. This study investigated whether common polymorphisms of the TNF locus and the two receptor genes, TNFRSF1A and TNFRSF1B, influence circulating levels of encoded proteins, and whether individual polymorphisms or extended haplotypes of these genes are associated with susceptibility, severity of illness or outcome in adult patients with severe sepsis or septic shock. A total of 213 Caucasian patients were recruited from eight intensive care units (ICU) in the UK and Australia. Plasma levels of TNF (P ¼ 0.02), sTNFRSF1A (P ¼ 0.005) and sTNFRSF1B (P ¼ 0.01) were significantly higher in those who died on ICU compared to those who survived. There was a positive correlation between increasing soluble receptor levels and organ dysfunction (increasing SOFA score) (sTNFRSF1A R ¼ 0.51, Po0.001; sTNFRSF1B R ¼ 0.53, Po0.001), and in particular with the degree of renal dysfunction. In this study, there were no significant associations between the selected candidate TNF or TNF receptor polymorphisms, or their haplotypes, and susceptibility to sepsis, illness severity or outcome. The influence of polymorphisms of the TNF locus on susceptibility to, and outcome from sepsis remains uncertain.

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Section: Discussioncontrasting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study

et al. 2004

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“…Similarly, Yen et al 30 included a healthy control group that showed very striking differences in allele frequencies to the patient population, but against a background of some confusion as to the true allele frequencies in the Taiwanese population. Two studies quoted lower but broadly similar allele frequencies 121,127 while one study reported allele frequencies among healthy controls that were similar to the patient group in the Yen et al study. 128 The problem of population stratification can be overcome by use of family-based studies such as the transmission disequilibrium test, 129 which are insensitive to population heterogeneity, or by applying methods to detect population stratification.…”

Section: Disease Associations-conclusionmentioning

confidence: 72%

“…Similarly, a US study 120 that looked at the occurrence of severe sepsis after trauma in 37 patients found that the A allele was associated with both occurrence of sepsis (OR 4.6, CI 1.9-10.9) and death (OR 2.1, CI 0.6-7.3). These findings were only partly confirmed in a Taiwanese study 121 involving 42 patients with septic shock. Here, it was found that while the A allele was not more common in patients with septic shock, carriage of the allele did result in an increased risk of death (92 vs 62%, Po0.05).…”

Section: Leprosymentioning

confidence: 93%

Is there a future for TNF promoter polymorphisms?

2004

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The in vitro study of TNF promoter polymorphism (SNP) function was stimulated by the numerous case-control (association) studies of the polymorphisms in relation to human disease and the appearance of several studies claiming to show a functional role for these SNPs provided a further impetus to researchers interested in the role of TNF in their disease of interest. In this review we consider case-control studies, concentrating on the autoimmune and inflammatory diseases rheumatoid arthritis, multiple sclerosis, ankylosing spondylitis, and asthma, and on infectious diseases including malaria, hepatitis B and C infection, leprosy and sepsis/septic shock. We also review the available evidence on the functional role of the various TNF promoter polymorphisms. In general, case-control studies have produced mixed results, with little consensus in most cases on whether any TNF polymorphisms are actually associated with disease, although results have been more consistent in the case of infectious diseases, particularly malaria. Functional studies have also produced mixed results but recent work suggests that the much studied À308G/A polymorphism is not functional, while the function of other TNF polymorphisms remains controversial. Studies of the TNF region are increasingly using extended haplotypes that can better capture the variation of the MHC region.

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“…Studies performed in children with meningococcal disease [112], in patients with septic shock [100,141], in old septic shock patients [143], and more recently in old patients affected by severe bronchus-alveolar infections [33], show that the TNF-a -308A allele (A+ carrier) is associated with adverse outcome with respect to TNF-a -308A allele (A-carrier). Moreover, patients with A+ carrier have less responsiveness to drugs and significantly increased risk of death [120].…”

Section: Zinc-tnf-a Gene Interactionsmentioning

confidence: 99%

Zinc–gene interaction related to inflammatory/immune response in ageing

Mocchegiani

Malavolta

2008

Genes Nutr

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The pivotal role played by zinc-gene interaction in affecting some relevant cytokines (IL-6 and TNF-a) and heat shock proteins (HSP70-2) in ageing, successful ageing (nonagenarians) and the most common age-related diseases, such as atherosclerosis and infections, is now recognized. The polymorphisms of genes codifying proteins related to the inflammation are predictive on one hand in longevity, on the other hand they are associated with atherosclerosis or severe infections. Since the health lifespan has a strong genetic component, which in turn also affected by nutritional factors like zinc, the association of these polymorphisms with innate immune response, zinc ion bioavailability and Metallothioneins (MT) homeostasis is an useful tool to unravel the role played by zinc-gene interactions in longevity, especially due to the inability of MT in zinc release in ageing and chronic inflammation. In ageing, this last fact leads to depressed innate immune response for host defence. In contrast, in very old age the inflammation is lower with subsequent more zinc ion bioavailability, less MT gene expression and satisfactory innate immunity. Therefore, the zinc-gene (IL-6, TNF-a, Hsp70-2) interactions, via MT homeostasis, are crucial to achieve successful ageing. Human genes and longevityAgeing is a universal phenomenon that affects nearly all of animal species. According to Helfand and Rogina [69], ageing can be characterized as: (1) an inevitable consequence of being a multicellular organism; (2) associated with a random, passive decline in function; (3) leading to a global loss of homeostasis over time and (4) mortality increasing with ageing. Evolutionary studies on ageing have drawn the attention on the importance of the genetic mechanisms involved in somatic maintenance and repair that secure longevity [82]. Evidence from model organisms has indicated that subtle variation in the genes can dramatically influence lifespan. However, findings on potential candidate genetic mechanisms determining ageing and lifespan in model organisms are far to explain variations in human populations because phenotypes are critically dependent on the setting in which genes are expressed, while laboratory conditions and modern environments are markedly dissimilar [86]. Genetic analysis of human ageing is mainly approached by searching the genetic basis of susceptibility to major geriatric disorders or the allelic contributions to exceptionally long life span. It is just thanks to these last studies in centenarians populations that several candidate longevity genes or pathways including PON1 [19,130], IGF1/insulin pathway [84,120], elements of lipid metabolism [12], stress response [34] and inflammatory response have been identified [53].Genes related to inflammation and stress response, in particular the pro-inflammatory cytokines IL-1, IL-6, TNFalpha, the anti-inflammatory cytokine IL-10, the HSP70 chaperones and the regulators of trace elements homeostasis, metallothioneins (MT), seem particularly relevant taking into accoun...

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Tumor necrosis factor gene polymorphism and septic shock in surgical infection

Cited by 163 publications

References 20 publications

TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study

TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study

Is there a future for TNF promoter polymorphisms?

Zinc–gene interaction related to inflammatory/immune response in ageing

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