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

Abstract

To investigate the association of eNOS 894G-->T, -786T-->C gene polymorphisms with disease severity and outcome in septic patients. 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. 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. Carriage of genotype GT in eNOS 894G-->T polymorphism is associated with the occurrence of shock and impaired organ function.