Linked Life Data

18182917

Source:http://linkedlifedata.com/resource/pubmed/id/18182917

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-1-9
pubmed:abstractText
Replication of statistically significant associations between single nucleotide polymorphisms (SNPs) and disease phenotypes has been problematic. One reason for conflicting observations may be failure to consider confounding factors, including gene-gene (epistatic) interactions. Our experience with the insertion/deletion polymorphism at -688 in the promoter region of plasminogen activator inhibitor (PAI-1) seems to support this contention and may foreshadow problems for genome-wide association scans, which tend to use unadjusted analytical methodologies. One hundred forty-nine patients with > or =15% total body surface area (TBSA) burns, without significant nonburn-related trauma (injury severity score < or =16), traumatic or anoxic brain injury or spinal cord injury who survived >48 hours postadmission were enrolled under a protocol approved by the UT Southwestern and Parkland Hospital IRBs. Clinical data were collected prospectively and candidate polymorphisms in PAI-1 (-688), toll-like receptor 4 (+896), CD14 (-159), tumor necrosis factor-alpha (-308), and interleukin-6 (-174) were genotyped. The PAI-1 SNP was significantly associated (P-value for trend = 0.036) with risk for death when evaluated in isolation by unadjusted analysis. However, after adjustment for potential confounders using multiple logistic regression, only age, full-thickness burn size, and CD14 genotype (as previously reported) were associated with increased mortality. Genetic association analyses should be adjusted for interactions between multiple SNPs, injury or disease characteristics, and demographic variables. Increasingly sophisticated analytical methods will be required as gene-mapping studies transition from a candidate-gene based approach to genome-wide association scans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:issn
1559-047X
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
168-75
pubmed:meshHeading
pubmed:articleTitle
Epistatic interactions are critical to gene-association studies: PAI-1 and risk for mortality after burn injury.
pubmed:affiliation
Surgery Department, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9160, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural