Epistatic interactions are critical to gene-association studies: PAI-1 and risk for mortality after burn injury.

摘要: 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 promoter region plasminogen activator inhibitor (PAI-1) seems support this contention foreshadow problems genome-wide association scans, which tend use unadjusted analytical methodologies. hundred forty-nine patients > or =15% total body surface area (TBSA) burns, without nonburn-related trauma (injury severity score 48 hours postadmission were enrolled under a protocol approved by UT Southwestern Parkland Hospital IRBs. Clinical data collected prospectively candidate PAI-1 (-688), toll-like receptor 4 (+896), CD14 (-159), tumor necrosis factor-alpha (-308), interleukin-6 (-174) genotyped. The SNP was significantly associated (P-value trend = 0.036) risk death when evaluated isolation analysis. However, after adjustment potential confounders using multiple logistic regression, only age, full-thickness burn size, genotype (as previously reported) increased mortality. Genetic analyses should adjusted interactions SNPs, injury characteristics, demographic variables. Increasingly sophisticated methods will required as gene-mapping studies transition from candidate-gene based approach scans.