内皮源性一氧化氮合酶基因多态性对脓毒症患者疾病严重程度及预后的影响

目的 探讨一氧化氮合酶(eNOS)894G→T,-786T→C基因多态性与脓毒症患者疾病严重程度及预后的相关性.方法 于2007年4月至2009年5月,在北京9个教学医院ICU随机收集严重脓毒症患者117例,应用PCR-RLFP及PCR-SSCP方法检测eNOS 894G→T,-786T→C等位基因和基因型.记录患者一般情况、致病微生物,入ICU后24 h内急性心理学与慢性健康状况评分系统Ⅱ(APACHE)Ⅱ评分、7 d内SOFA评分、感染性休克发生率、致休克时间(从发生感染至出现休克时间)、休克持续时间、人ICU后7及28 d病死率.结果 eNOS 894 G→T基因多态性中基因型GT携带者感染性休克的发生率较基因型GG携带者有增加趋势(87%vs 68.1%,P=0.071),且致休克时间明显缩短[1.0(0.1-6.5)d vs 2.0(0.10-27.0)d,中位数(范围),P<0.05].此类患者APACHE Ⅱ(24±7 vs 19±7)及序贯器官衰竭分析(SOFA)评分(9±3 vs 5±3)显著升高(P<0.05,P<0.001),7 d和28 d病死率显著增高(34.8%vs 0%,P<0.001;78.3%vs 23.4%,P<0.001).多因素分析发现,年龄、SOFA评分以及基因型GT为影响严重脓毒症预后的独立高危风险因素.本研究未发现eNOS 0786T→C基因多态性与脓毒症患者疾病严重程度及预后存在相关性.结论 eNOS 894C→T(而非-786T→C)基因多态性与脓毒症患者疾病严重程度及预后存在密切关系.基因型GT携带者器官功能损害更加显著,并且与感染性休克的发病过程关系密切.

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.