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The Synergy of ‐260 T T CD14 and ‐308 GG TNF‐α Genotypes in Survival of Critically Ill Patients
Author(s) -
Fallavena P. R. V.,
Jesus Borges T.,
Paskulin D. D.,
Thurow H. S.,
Oliveira Paludo F. J.,
Santos Froes C.,
Graebin P.,
Dias F. S.,
Toledo Nóbrega O.,
Alho C. S.
Publication year - 2013
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12002
Subject(s) - genotype , snp , hazard ratio , medicine , allele , survival analysis , critically ill , proportional hazards model , gastroenterology , biology , single nucleotide polymorphism , genetics , gene , confidence interval
Literature suggests that the analysis of several polymorphic genetic markers is more informative than the analysis of a single polymorphism. In this study, we tested whether the shared inheritance of TLR2 and TLR4 and TNF‐α allelic variants may act in synergy with ‐260C> T CD14 SNP on the outcome from critical conditions. We monitored 524 critically ill patients from S outh B razilian, daily from the ICU admission to their discharge from hospital, or death. Our results revealed that TLR2 , TLR4 or TNF‐α SNP s alone did not show a significant role in the outcome from critical illness. However, when we performed a combined analysis with the CD14 inheritance, we detected a significant higher survivor rate in ‐260 TT CD14/ ‐308 GG TNF‐α individuals ( P = 0.037). In the adjusted analysis including the main clinical predictors to mortality, we observed that ‐260 TT / ‐308 GG double‐genotype was a significant protective factor towards survival ( P = 0.046). An increased probability for survival of ‐260 TT / ‐308 GG was also observed by ‘pathway genetic load’ analysis (unweighted: P = 0.041; weighted: P = 0.036). When we applied a hazard function analysis with the ‐260 TT / ‐308 GG variable as a discriminating factor, ‐260 TT /‐308 GG patients group had, in fact, a higher survivor rate ( P = 0.024). Connected to the beneficial effect of ‐260 TT CD14 , the ‐308 GG TNF‐α genotype was protective against the reported over expression of TNF‐α caused by ‐308A rare allele. Results support the hypothesis that the interaction between ‐260C>T CD14 and ‐308G>A TNF‐α functional SNP s may be synergistically influencing the outcome of critically ill patients.