Linked Life Data

21257964

Source:http://linkedlifedata.com/resource/pubmed/id/21257964

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2011-2-3
pubmed:abstractText
We tested the hypothesis that single nucleotide polymorphisms (SNPs) within genes of the NF-?B pathway are associated with altered clinical outcome of septic shock patients. We genotyped 59 SNPs in the NF-?B pathway in a discovery cohort of septic shock patients (St. Paul's Hospital [SPH], N = 589), which identified the C allele of rs7222094 T/C within MAP3K14 (NF-?B inducing kinase; NIK) associated with increased 28-d mortality (uncorrected p = 0.00024, Bonferroni corrected p = 0.014). This result was replicated in a second cohort of septic shock patients (Vasopressin and Septic Shock Trial [VASST; N = 616]) in which the CC genotype of rs7222094 was associated with increased 28-d mortality (Cox regression: SPH cohort hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.12-1.64; p = 0.002 Caucasian only; and VASST cohort HR, 1.24; 95% CI, 1.00-1.52; p = 0.048 Caucasian only). Patients having the CC genotype of rs7222094 in SPH experienced more renal and hematological dysfunction (p = 0.003 and p = 0.011), while patients of the VASST cohort with the rs7222094 CC genotype showed the same trend toward more renal dysfunction. In lymphoblastoid cell lines, we found the rs7222094 genotype most strongly associated with mRNA expression of CXCL10, a chemokine regulated by NF-?B. Accordingly, we measured CXCL10 protein levels and found that the CC genotype of rs7222094 was associated with significantly lower levels than those of the TT genotype in lymphoblastoid cell lines (p < 0.05) and in septic shock patients (p = 0.017). This suggests that the CC genotype of NIK rs7222094 is associated with increased mortality and organ dysfunction in septic shock patients, perhaps due to altered regulation of NF-?B pathway genes, including CXCL10.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2321-8
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
A single nucleotide polymorphism in NF-?B inducing kinase is associated with mortality in septic shock.
pubmed:affiliation
University of British Columbia Critical Care Research Laboratories, Heart and Lung Institute, St. Paul's Hospital, Vancouver, British Columbia V6Z 1Y6, Canada.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't