J Innate Immun. 2018;10(3):181-188. doi: 10.1159/000486104. Epub 2018 Jan 16.
The IL10 family of genes includes crucial immune regulators. We tested the hypothesis that single nucleotide polymorphisms (SNPs) in IL10, IL19, IL20, and IL24 of the IL10 family gene cluster alter the clinical outcome of septic shock.
Patients with septic shock (n = 1,193) were genotyped for 13 tag SNPs of IL10, IL19, IL20, and IL24. IL20 gene expression was measured in genotyped lymphoblastoid cells in vitro. Cardiac surgical ICU patients (n = 981) were genotyped for IL20 rs2981573 A/G. The primary outcome variable was 28-day mortality.
Patients with the G allele of IL20 rs2981573 had a significantly increased hazard of death over the 28-day period compared to patients with the A allele in the septic shock cohort (adjusted hazard ratio 1.27; 95% confidence interval 1.10-1.47; p = 8.0 × 10-4). Patients with the GG genotype had more organ dysfunction (p < 0.05). The GG genotype was associated with increased IL20 gene expression in stimulated lymphoblastoid cells in vitro (p < 0.05). The cardiac surgical ICU patients with the GG genotype had an increased length of ICU stay (p = 0.032).
The GG genotype of IL20 rs2981573 SNP was associated with increased IL20 gene expression and increased adverse outcomes in patients with septic shock and following cardiac surgery.
IL10 家族基因包括关键的免疫调节因子。我们检验了这样一个假设,即 IL10、IL19、IL20 和 IL24 家族基因簇中的单核苷酸多态性(SNP)改变了脓毒性休克的临床结局。
对 1193 例脓毒性休克患者进行了 IL10、IL19、IL20 和 IL24 家族基因簇中 13 个标签 SNP 的基因分型。在体外对基因分型的淋巴母细胞中测量了 IL20 基因表达。对心脏外科 ICU 患者(n=981)进行了 IL20 rs2981573A/G 的基因分型。主要观察变量是 28 天死亡率。
与脓毒性休克患者中 IL20 rs2981573 的 A 等位基因相比,G 等位基因的患者在 28 天期间死亡的风险显著增加(调整后的危险比 1.27;95%置信区间 1.10-1.47;p=8.0×10-4)。GG 基因型患者的器官功能障碍更多(p<0.05)。GG 基因型与体外刺激的淋巴母细胞中 IL20 基因表达增加有关(p<0.05)。GG 基因型的心脏外科 ICU 患者 ICU 住院时间延长(p=0.032)。
IL20 rs2981573 SNP 的 GG 基因型与脓毒性休克和心脏手术后患者 IL20 基因表达增加和不良结局增加有关。