Effect of endothelial nitric oxide synthase gene polymorphisms upon disease severity and outcome in septic patients

Objective To investigate the association of eNOS 894G→T, -786T→C gene polymorphisms with disease severity and outcome in septic patients. Methods A total of 117 patients with severe sepsis were randomly selected from ICUs at 9 academic hospitals in Beijing during April 2007 to May 2009. PCR-RFLP and PCR-SSCP were used to analyze the alleles and genotypes in eNOS 894G→T and - 786T→C gene polymorphisms. Recorded clinical data included demographics, pathogens, APACHE Ⅱ score within 24 hours and SOFA score within 7 days after ICU admission, percentage of shock patients, days to shock onset (from infection to shock onset ), duration of shock and the mortality at Days 7 and 28. Results In comparison with genotype GT carriers, the patients with genotype GT in eNOS 894G→T polymorphism had a incremental trend in frequency of shock (87% vs 68. 1 % , P = 0. 071) and a significantly shortened days to shock onset [1. 0(0.1-6. 5)vs 2. 0 (0.10-27.0) days, median (range), P<0.05]. Those patients had been shown to have a significantly high APACHE Ⅱ score (23. 61 ± 7. 00 vs 19. 50 ± 6.99, P<0.05), SOFA score(9. 43 ±3.42 vs 5. 26 ±2. 94 , P <0.001)and mortality at Day 7 (34.8% vs 0% , P <0. 001) and Day 28 (78. 3% vs 23. 4% , P <0.001). Multivariate analyses revealed that age in years, SOFA score and genotype GT in eNOS 894G→T polymorphism were independent high-risk factors for the outcome in septic patients. However, eNOS -786T→C gene polymorphism was not associated with disease severity and outcome in septic patients. Conclusion Carriage of genotype GT in eNOS 894G→T polymorphism is associated with the occurrence of shock and impaired organ function. Key words: Sepsis; Nitric-oxide synthase; Gene; Prognosis