BACKGROUND: The outcome of patients with trauma does not always correlate with injury severity or premorbid health status. This study evaluates the relationship between polymorphisms in the first intron of the interferon-gamma gene and the development of sepsis after trauma. METHODS: DNA was extracted from peripheral leukocytes of patients with trauma and an injury severity score of 16 or greater. Data collected included demographics, injury mechanism, injuries sustained, development of sepsis, and outcome. A previously identified cytosine/adenine repeated polymorphism was amplified, alleles/genotypes identified, and the results correlated with patient outcome. RESULTS: Sixty-one patients were evaluated. Thirty patients (49%) became septic. The injury severity score, race, age, and gender distribution was similar for both the septic and nonseptic groups. Six alleles and 10 genotypes were identified. Alleles C (34%) and D (52%) were the most common. Patients who were septic had a 62% chance of having a D allele (P =.06), whereas they had only a 29% chance of having a C allele. Homozygotes for allele D (DD) were the most likely to become septic (65%). CONCLUSIONS: Homozygotes for the D allele (DD) of the interferon-gamma gene have an increased chance of developing sepsis after traumatic injury compared with other allelic combinations. This supports the hypothesis that genetic composition plays a role in patient outcome.
BACKGROUND: The outcome of patients with trauma does not always correlate with injury severity or premorbid health status. This study evaluates the relationship between polymorphisms in the first intron of the interferon-gamma gene and the development of sepsis after trauma. METHODS: DNA was extracted from peripheral leukocytes of patients with trauma and an injury severity score of 16 or greater. Data collected included demographics, injury mechanism, injuries sustained, development of sepsis, and outcome. A previously identified cytosine/adenine repeated polymorphism was amplified, alleles/genotypes identified, and the results correlated with patient outcome. RESULTS: Sixty-one patients were evaluated. Thirty patients (49%) became septic. The injury severity score, race, age, and gender distribution was similar for both the septic and nonseptic groups. Six alleles and 10 genotypes were identified. Alleles C (34%) and D (52%) were the most common. Patients who were septic had a 62% chance of having a D allele (P =.06), whereas they had only a 29% chance of having a C allele. Homozygotes for allele D (DD) were the most likely to become septic (65%). CONCLUSIONS: Homozygotes for the D allele (DD) of the interferon-gamma gene have an increased chance of developing sepsis after traumatic injury compared with other allelic combinations. This supports the hypothesis that genetic composition plays a role in patient outcome.
Authors: B D Freeman; C R Kennedy; H L Frankel; B Clarridge; D Bolcic-Jankovic; E Iverson; E Shehane; A Celious; B A Zehnbauer; T G Buchman Journal: Pharmacogenomics J Date: 2009-12-08 Impact factor: 3.550
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