About: Genetic Variation in the TNF Gene Is Associated with Susceptibility to Severe Sepsis, but Not with Mortality

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About: Genetic Variation in the TNF Gene Is Associated with Susceptibility to Severe Sepsis, but Not with Mortality Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Genetic Variation in the TNF Gene Is Associated with Susceptibility to Severe Sepsis, but Not with Mortality
Creator	Gao, Lei Zhang, Yong Bai, Chunxue Jiang, Jinjun Shen, Qinjun Shen, Yao Song, Yuanlin Song, Zhenju Sun, Zhan Tong, Chaoyang Yao, Chenling Yin, Jun Zhu, Duming
Source	PMC
abstract	BACKGROUND: Tumor necrosis factor (TNF) and TNF receptor superfamily (TNFR)-mediated immune response play an essential role in the pathogenesis of severe sepsis. Studies examining associations of TNF and lymphotoxin-α (LTA) single nucleotide polymorphisms (SNPs) with severe sepsis have produced conflicting results. The objective of this study was to investigate whether genetic variation in TNF, LTA, TNFRSF1A and TNFRSF1B was associated with susceptibility to or death from severe sepsis in Chinese Han population. METHODOLOGY/PRINCIPAL FINDINGS: Ten SNPs in TNF, LTA, TNFRSF1A and TNFRSF1B were genotyped in samples of patients with severe sepsis (n = 432), sepsis (n = 384) and healthy controls (n = 624). Our results showed that rs1800629, a SNP in the promoter region of TNF, was significantly associated with risk for severe sepsis. The minor allele frequency of rs1800629 was significantly higher in severe sepsis patients than that in both healthy controls (P(adj) = 0.00046, odds ratio (OR)(adj) = 1.92) and sepsis patients (P(adj) = 0.002, OR(adj) = 1.56). Further, we investigated the correlation between rs1800629 genotypes and TNF-α concentrations in peripheral blood mononuclear cells (PBMCs) of healthy volunteers exposed to lipopolysaccharides (LPS) ex vivo, and the association between rs1800629 and TNF-α serum levels in severe sepsis patients. After exposure to LPS, the TNF-α concentration in culture supernatants of PBMCs was significantly higher in the subjects with AA+AG genotypes than that with GG genotype (P = 0.007). Moreover, in patients with severe sepsis, individuals with AA+AG genotypes had significantly higher TNF-α serum concentrations than those with GG genotype (P(adj) = 0.02). However, there were no significant associations between SNPs in the four candidate genes and 30 day mortality for patients with severe sepsis. CONCLUSIONS/SIGNIFICANCE: Our findings suggested that the functional TNF gene SNP rs1800629 was strongly associated with susceptibility to severe sepsis, but not with lethality in Chinese Han population.
has issue date	2012-09-27(xsd:dateTime)
bibo:doi	10.1371/journal.pone.0046113
bibo:pmid	23029405
has license	cc-by
sha1sum (hex)	d077e86d41dd4161565d2edf1446d8bc4ec5ed0a
schema:url	https://doi.org/10.1371/journal.pone.0046113
resource representing a document's title	Genetic Variation in the TNF Gene Is Associated with Susceptibility to Severe Sepsis, but Not with Mortality
has PubMed Central identifier	PMC3459853
has PubMed identifier	23029405
schema:publication	PLoS One
resource representing a document's body	covid:d077e86d41dd4161565d2edf1446d8bc4ec5ed0a#body_text
is schema:about of	named entity 'ASSOCIATED WITH' named entity 'TNFRSF1A' named entity 'SUSCEPTIBILITY' named entity 'GENETIC VARIATION' named entity 'OBJECTIVE' named entity 'PATHOGENESIS' named entity 'CONFLICTING' named entity 'TUMOR NECROSIS FACTOR ' named entity 'TO INVESTIGATE' named entity 'TNF RECEPTOR SUPERFAMILY' named entity 'CHINESE' named entity 'HAN' named entity 'SUSCEPTIBILITY' named entity 'HAVE' named entity 'BUT' named entity 'SEVERE SEPSIS' named entity 'DEATH' named entity 'MORTALITY' named entity 'SEVERE SEPSIS' named entity 'MEDIATED' named entity 'POPULATION' named entity 'GENETIC VARIATION' named entity 'RESULTS' named entity 'LTA' named entity 'ASSOCIATED WITH' named entity 'STUDY' named entity 'TNF' named entity 'SINGLE NUCLEOTIDE POLYMORPHISMS' named entity 'IMMUNE RESPONSE' named entity 'ESSENTIAL' named entity 'PLAY' named entity 'BACKGROUND' named entity 'STUDIES' named entity 'LYMPHOTOXIN-A' named entity 'TNF GENE' named entity 'EXAMINING' named entity 'ASSOCIATIONS' named entity 'ROLE' named entity 'TNFRSF1B' covid:arg/d077e86d41dd4161565d2edf1446d8bc4ec5ed0a named entity 'Tumor necrosis factor' named entity 'TNF receptor superfamily' named entity 'TNF' named entity 'Genetic Variation' named entity 'sepsis' named entity 'TNFRSF1B' named entity 'polymorphisms' named entity 'genotypes' named entity 'incubation' named entity 'Ficoll' named entity 'systematic review' named entity 'genotype' named entity 'TNF-a' named entity 'TNFRSF1B' named entity 'promoter region' named entity 'PBMCs' named entity 'Student's t-test' named entity 'severe sepsis' named entity 'plasma' named entity 'multivariate analyses' named entity 'Crohn's disease' named entity 'sepsis' named entity 'severe sepsis' named entity 'infection' named entity 'supernatants' named entity 'rs1800629' named entity 'genetic variation' named entity 'control group' named entity 'serum levels'

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