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

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

目的探讨一氧化氮合酶（eNOS）894G→T，一786T→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eNOS894G→T，一786T→C等位基因和基因型。记录患者一般情况、致病微生物，人ICU后24h内急性心理学与慢性健康状况评分系统Ⅱ（APACHE）11评分、7d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、入ICU后7及28d病死率。结果eNOS894G→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％VS68．1％，P=0．071），且致休克时间明显缩短[1．0（0．1～6．5）dVS2．0（0．10～27．0）d，中位数（范围），P〈0．05]。此类患者APACHEII（24±7vs19±7）及序贯器官衰竭分析（SOFA）评分（9±3vs5±3）显著升高（P〈0．05，P〈0．001），7d和28d病死率显著增高（34．8％vs0％，P〈0．001；78．3％vs23．4％，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eNOS0786T→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eNOS894→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。

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 Ⅱscore （23.61 ± 7.00 vs 19. 50 ± 6. 99, P 〈 0. 05 ）, SOFA seore （ 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 septie patients. Conclusion Carriage of genotype GT in eNOS 894G→T polymorphism is associated with the oecurrence of shoek and impaired organ function.