Department of Nephrology Ward, Zibo Central Hospital, Zhangdian, Zibo, Shandong.
Department of Emergency Medicine Department, People's Hospital of Tiantai County, Tiantai County, Taizhou City, Zhejiang, China.
Medicine (Baltimore). 2021 Jul 2;100(26):e26293. doi: 10.1097/MD.0000000000026293.
To investigate the relationship between thrombomodulin (THBD) gene single nucleotide polymorphisms (SNPs) and susceptibility to sepsis and the occurrence and prognosis of acute kidney injury (AKI) in sepsis patients.The genotypes of THBD gene rs1962, rs3176123, and rs1042580 in 178 sepsis patients with AKI, 243 sepsis patients without AKI (No AKI), and 103 healthy controls were analyzed by direct sequencing. Enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma THBD protein levels. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value of plasma THBD levels in sepsis, AKI, and death of sepsis patients.The C allele carriers of THBD gene rs1962 were more likely to develop AKI and sepsis than the T allele carriers (OR = 1.61, 95% CI: 1.18-2.19, P < .01; OR = 2.16, 95% CI: 1.42-3.29, P < .01). The rs3176123 G allele was associated with an increased risk of AKI in sepsis patients (OR = 1.41, 95% CI: 1.06-1.88, P = .02), the G allele had a significant association with a higher risk of sepsis susceptibility (OR = 1.91, 95% CI: 1.33-2.75, P < .01). Sepsis patients of rs1042580 C allele had a lower risk of AKI than those of T allele (OR = 0.58, 95% CI: 0.37-0.91, P = .02), the C allele was related to a reduced risk of sepsis susceptibility (OR = 0.38, 95% CI: 0.26-0.55, P < .01). The THBD gene rs1962, rs3176123, and rs1042580 TGT haplotype was linked to higher risk of AKI in patients with sepsis (OR = 1.96, 95%CI: 1.14-3.38, P = .02). Sepsis patients with the THBD gene rs1962 TC + CC genotype had a higher risk of death than those with TT genotype (OR = 10.93, 95%CI: 5.05-26.96, P < .01), but there was no significant difference in the risk of death in sepsis patients with different genotypes at rs3176123 and rs1042580 (P > .05).The THBD gene rs1962, rs3176123, and rs1042580 SNPs are significantly associated with sepsis susceptibility and the risk of AKI. The rs1962 SNP is related to the risk of death in sepsis patients.
探讨血栓调节蛋白（THBD）基因单核苷酸多态性（SNP）与脓毒症易感性、脓毒症患者急性肾损伤（AKI）的发生和预后的关系。方法：采用直接测序法对 178 例 AKI 脓毒症患者、243 例无 AKI（非 AKI）脓毒症患者和 103 例健康对照者的 THBD 基因 rs1962、rs3176123 和 rs1042580 基因型进行分析。采用酶联免疫吸附试验（ELISA）检测血浆 THBD 蛋白水平。采用受试者工作特征（ROC）曲线分析评估血浆 THBD 水平对脓毒症、AKI 和脓毒症患者死亡的诊断价值。结果：THBD 基因 rs1962 的 C 等位基因携带者比 T 等位基因携带者更容易发生 AKI 和脓毒症（OR=1.61，95%CI：1.18-2.19，P<0.01；OR=2.16，95%CI：1.42-3.29，P<0.01）。rs3176123 的 G 等位基因与脓毒症患者 AKI 风险增加相关（OR=1.41，95%CI：1.06-1.88，P=0.02），G 等位基因与脓毒症易感性的风险显著增加相关（OR=1.91，95%CI：1.33-2.75，P<0.01）。rs1042580 的 C 等位基因携带者发生 AKI 的风险低于 T 等位基因携带者（OR=0.58，95%CI：0.37-0.91，P=0.02），C 等位基因与脓毒症易感性的风险降低相关（OR=0.38，95%CI：0.26-0.55，P<0.01）。THBD 基因 rs1962、rs3176123 和 rs1042580 的 TGT 单倍型与脓毒症患者 AKI 的风险增加相关（OR=1.96，95%CI：1.14-3.38，P=0.02）。与 TT 基因型相比，rs1962 基因型为 TC+CC 的脓毒症患者死亡风险更高（OR=10.93，95%CI：5.05-26.96，P<0.01），但 rs3176123 和 rs1042580 不同基因型的脓毒症患者死亡风险无显著差异（P>0.05）。结论：THBD 基因 rs1962、rs3176123 和 rs1042580 SNP 与脓毒症易感性和 AKI 风险显著相关。rs1962 SNP 与脓毒症患者的死亡风险相关。
