汉族人群诱导性一氧化氮合酶T-786C、G894T基因多态性与脓毒症易感性的关系

Relationship between eNOS T-786C,G894T polymorphisms and susceptibility to sepsis in Chinese Han population

目的探索汉族人群内皮型一氧化氮合酶(eNOS)T-786C、G894T基因多态性中对脓毒症存在易感的高风险等位基因或基因型。方法2007年4月-2009年5月,在北京9家教学医院ICU随机收集脓毒症患者117例,并招募健康志愿者100名作为对照,应用PCR-SSCP及PCR-RLFP方法检测eNOST-786C、G894T的等位基因和基因型。结果脓毒症患者与健康人群之间eNOST-786C及G894T各等位基因或基因型的发生频率无显著差异(P>0.05)。但脓毒症患者中TC基因型的出现频率(30.8%)与健康人群(24.0%)相比有增加趋势(P=0.086);等位基因C携带者的比例(18.8%)高于健康人群(12.0%),但未达到统计学差异(P=0.052)。117例脓毒症患者中发现4例CC纯合子基因型个体,占3.4%;健康对照组中未发现CC纯合子基因型个体。结合既往文献结果进行分析发现,eNOS T-786C和G894T各基因型的出现频率存在种族差异,与白种人比较,亚洲黄种人eNOS T-786C基因型TC、CC以及G894T基因型GT、TT的出现频率均显著降低(P=0.000)。结论eNOS T-786C等位基因C或基因型TC的携带人群对脓毒症可能存在易感趋势,而G894T基因多态性与脓毒症易感性无密切关系。

Objective To investigate the relationship between the high risk alleles or genotypes of endothelial nitric oxide synthase （eNOS） polymorphism （T-786C and G894T） and the susceptibility to sepsis in Chinese Han population. Methods One hundred and seventeen septic patients were randomly selected from ICUs of 9 academic hospitals in Beijing during Apr. 2007 to May 2009. A hundred healthy volunteers were recruited as control. PCR-RFLP and PCR-SSCP were used to analyze the alleles and genotypes in eNOS T-786C and G894T polymorphisms. Results No significant difference was found in the frequency of specific allele or genotype in T-786C or G894T eNOS gene polymorphisms between septic patients and healthy volunteers in present study （P0.05）. However, the frequency of genotype TC in T-786C showed an increasing trend among patients with sepsis （30.8% vs 24.0%, P=0.086）. The percentage of allele C carrier was higher in patients with sepsis, but there was no significant difference between two groups （18.8% vs 12.0%, P=0.052）. In addition, 4 cases of genotype CC homozygote were found in septic patients （3.4%）, but no homozygote CC genotype was found in healthy volunteers. According to previous publications in corroboration with our data, it was found that a difference in genotype frequency of both eNOS T-786C and G894T polymorphisms existed in different races. Compared with Caucasian, the frequencies of genotype TC and CC in T-786C, and GT and TT in G894T were significantly lower in Asian （P=0.000）. Conclusions Population with the carriage of allele C or genotype TC in T-786C eNOS gene polymorphism may have the risk of susceptibility to sepsis. Whereas, the eNOS G894T polymorphism is unlikely to be associated with the susceptibility to sepsis.