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Genetic polymorphisms and posttraumatic complications.

ABSTRACT: Major trauma is the leading cause of death in young adults. Despite advances in prehospital system and treatment in hospital, mortality rates have not improved significantly over the past decades. Victims of severe injuries who survive the initial hours have great risk for additional life-threatening complicaitons, including uncontrollable infection (sepsis) and multiple organ dysfunction syndrome (MODS). Single nucleotide polymorphisms (SNPs) have been shown to affect susceptibility to the course of numerous diseases. Accumulating evidence suggests that genetic backgrounds also play important roles in posttraumatic complications. Genetic polymorphisms may become powerful biomarkers for diagnosis and prognosis of trauma-induced complications. Recent advances in studies on associations between genetic polymorphisms and sepsis or MODS have led to better understanding of posttraumatic complications. Here we summarise recent findings on genetic variations in molecules of the innate immune system and other systems as well as their connection with susceptibility to posttraumatic complications.

SUBMITTER: Gu W

PROVIDER: S-EPMC3025375 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Genetic polymorphisms and posttraumatic complications.

Gu Wei W Jiang Jianxin J

Comparative and functional genomics 20100101

Major trauma is the leading cause of death in young adults. Despite advances in prehospital system and treatment in hospital, mortality rates have not improved significantly over the past decades. Victims of severe injuries who survive the initial hours have great risk for additional life-threatening complicaitons, including uncontrollable infection (sepsis) and multiple organ dysfunction syndrome (MODS). Single nucleotide polymorphisms (SNPs) have been shown to affect susceptibility to the cour ...[more]

PMID: 21274447

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Project description:This study aimed to investigate the effects of genetic variants and haplotypes in the renin-angiotensin system (RAS) on the risk of warfarin-induced bleeding complications at therapeutic international normalized ratios (INRs). Four single nucleotide polymorphisms (SNPs) of AGT, two SNPs of REN, three SNPs of ACE, four SNPs of AGTR1, and one SNP of AGTR2, in addition to VKORC1 and CYP2C9 variants, were investigated. We utilized logistic regression and several machine learning methods for bleeding prediction. The study included 142 patients, among whom 21 experienced bleeding complications. We identified a haplotype, H2 (TCG), carrying three SNPs of ACE (rs1800764, rs4341, and rs4353), which showed a significant relation with bleeding complications. After adjusting covariates, patients with H2/H2 experienced a 0.12-fold (95% CI 0.02-0.99) higher risk of bleeding complications than the others. In addition, G allele carriers of AGT rs5050 and A allele carriers of AGTR1 rs2640543 had 5.0- (95% CI 1.8-14.1) and 3.2-fold (95% CI 1.1-8.9) increased risk of bleeding complications compared with the TT genotype and GG genotype carriers, respectively. The AUROC values (mean, 95% CI) across 10 random iterations using five-fold cross-validated multivariate logistic regression, elastic net, random forest, support vector machine (SVM)-linear kernel, and SVM-radial kernel models were 0.732 (0.694-0.771), 0.741 (0.612-0.870), 0.723 (0.589-0.857), 0.673 (0.517-0.828), and 0.680 (0.528-0.832), respectively. The highest quartile group (≥75th percentile) of weighted risk score had approximately 12.0 times (95% CI 3.1-46.7) increased risk of bleeding, compared to the 25-75th percentile group, respectively. This study demonstrated that RAS-related polymorphisms, including the H2 haplotype of the ACE gene, could affect bleeding complications during warfarin treatment for patients with mechanical heart valves. Our results could be used to develop individually tailored intervention strategies to prevent warfarin-induced bleeding.

Dataset Information

Genetic polymorphisms and posttraumatic complications.

Publications

Genetic polymorphisms and posttraumatic complications.

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