Baghel Kavita, Srivastava Rajeshwar Nath, Chandra Abhijit, Goel Sudhir K, Agrawal Jyotsna, Kazmi Hasan Raza, Raj Saloni
Department of Surgical Gastroenterology, King George's Medical University, Lucknow, 226003, India,
J Gastrointest Surg. 2014 Aug;18(8):1486-94. doi: 10.1007/s11605-014-2574-5. Epub 2014 Jun 19.
Early prediction of postoperative sepsis remains an enormous clinical challenge. Association of TNF-α-308 G/A polymorphism with sepsis remains controversial. We, therefore, investigated this polymorphism with serum levels of cytokines TNF-α, IL-6, and IL-8 in relation to development of sepsis following major gastrointestinal surgery.
Two hundred and thirty-nine patients undergoing major gastrointestinal surgery were enrolled. Polymorphism was studied through the analysis of restriction fragments of Nco1-digested DNA with the polymerase chain reaction. All patients were followed for 1 month following surgery for evidence of sepsis. Levels of serum cytokines TNF-α, IL-6, and IL-8 were measured preoperatively and postoperatively by enzyme-linked immunosorbent assay (ELISA).
Forty-seven (19.66 %) patients developed postoperative sepsis. Patients with postoperative sepsis were significantly (p = 0.002) more likely to possess AA homozygous genotype with higher capacity to produce cytokines TNF-α (p < 0.0001), IL-6 (p < 0.0001), and IL-8 (p < 0.0001) as compared to other genotypes. When compared with patients carrying at least one G allele, the AA genotype was associated with a significantly higher probability (odds ratio (OR) = 4.17; p = 0.003; 95 % confidence interval (CI) = 1.5-11.48) of developing sepsis. Compared with the GG genotype, AA was associated with a significantly higher probability (OR = 5.18; p = 0.0008; 95 % CI = 1.82-14.76) of sepsis development.
TNF-α-308 G/A polymorphism is significantly associated with the development of postoperative sepsis and with increased expression of cytokines TNF-α, IL-6, and IL-8.
术后脓毒症的早期预测仍然是一项巨大的临床挑战。肿瘤坏死因子-α（TNF-α）-308 G/A多态性与脓毒症的关联仍存在争议。因此，我们研究了这种多态性与主要胃肠道手术后脓毒症发生发展相关的细胞因子TNF-α、白细胞介素-6（IL-6）和白细胞介素-8（IL-8）血清水平之间的关系。
纳入239例接受主要胃肠道手术的患者。通过聚合酶链反应分析经Nco1酶切的DNA的限制性片段来研究多态性。所有患者术后随访1个月，以寻找脓毒症证据。术前和术后通过酶联免疫吸附测定（ELISA）测量血清细胞因子TNF-α、IL-6和IL-8的水平。
47例（19.66%）患者发生术后脓毒症。与其他基因型相比，术后发生脓毒症的患者更有可能拥有AA纯合基因型，其产生细胞因子TNF-α（p<0.0001）、IL-6（p<0.0001）和IL-8（p<0.0001）的能力更高。与携带至少一个G等位基因的患者相比，AA基因型发生脓毒症的概率显著更高（优势比（OR）=4.17；p=0.003；95%置信区间（CI）=1.5-11.48）。与GG基因型相比，AA基因型发生脓毒症的概率显著更高（OR=5.18；p=0.0008；95%CI=1.82-14.76）。
TNF-α-308 G/A多态性与术后脓毒症的发生发展以及细胞因子TNF-α、IL-6和IL-8表达增加显著相关。
