Department of Medicine, Division of Nephrology, Kidney and Dialysis Research Laboratory, St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass., USA.
Nephron Clin Pract. 2013;123(1-2):67-73. doi: 10.1159/000351684. Epub 2013 Jun 21.
Tumor necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the pathobiology of acute kidney injury (AKI).
We explored the association of a functional polymorphism in the promoter region (rs1800629) of the TNFA gene with severity of AKI, as defined by level of glomerular filtration (serum cystatin C and creatinine) and tubular injury (urinary NAG, KIM-1, α-GST, and π-GST) markers, in 262 hospitalized adults.
In unadjusted analyses, compared with the GG genotype, the TNFA GA and AA genotype groups tended to have higher enrollment (p = 0.08), peak (p = 0.004), and discharge (p = 0.004) serum creatinine levels, and the AA genotype tended to have a higher enrollment serum cystatin C level (p = 0.04). Compared with the GG genotype, the TNFA GA and AA genotype groups tended to have a higher urinary KIM-1 level (p = 0.03), and the AA genotype group tended to have a higher urinary π-GST level (p = 0.03). After adjustment for sex, race, age, baseline estimated glomerular filtration rate, sepsis, and dialysis requirement, compared with the GG genotype, the TNFA minor A-allele group had a higher peak serum creatinine of 1.03 mg/dl (0.43, 1.63; p = 0.001) and a higher urinary KIM-1 (relative ratio: 1.73; 95% CI: 1.16, 2.59; p = 0.008). The TNFA minor A-allele group also had a higher Multiple Organ Failure score of 0.26 (95% CI: 0.03, 0.49; p = 0.024) after adjustment for sex, race, age, and sepsis.
The TNFA rs1800629 gene polymorphism is associated with markers of kidney disease severity and distant organ dysfunction among patients with AKI. Larger studies are needed to confirm these relationships.
肿瘤坏死因子-α（TNF-α）是一种促炎细胞因子，它与急性肾损伤（AKI）的病理生理学有关。
我们探讨了 TNF 基因启动子区域（rs1800629）的功能多态性与 AKI 严重程度的相关性，AKI 严重程度通过肾小球滤过（血清胱抑素 C 和肌酐）和肾小管损伤（尿 NAG、KIM-1、α-GST 和 π-GST）标志物来定义，该研究纳入了 262 名住院成人患者。
在未校正分析中，与 GG 基因型相比，GA 和 AA 基因型组的患者入组时（p = 0.08）、峰值时（p = 0.004）和出院时（p = 0.004）的血清肌酐水平更高，AA 基因型组的患者入组时的血清胱抑素 C 水平也更高（p = 0.04）。与 GG 基因型相比，GA 和 AA 基因型组的患者尿 KIM-1 水平更高（p = 0.03），AA 基因型组的患者尿 π-GST 水平也更高（p = 0.03）。在校正了性别、种族、年龄、基线估计肾小球滤过率、脓毒症和透析需求后，与 GG 基因型相比，TNF-α 次要 A 等位基因组的患者的峰值血清肌酐更高（1.03mg/dl，0.43，1.63；p = 0.001），尿 KIM-1 更高（相对比：1.73；95%CI：1.16，2.59；p = 0.008）。在校正了性别、种族、年龄和脓毒症后，TNF-α 次要 A 等位基因组的患者的多器官衰竭评分也更高（0.26，95%CI：0.03，0.49；p = 0.024）。
TNF-α rs1800629 基因多态性与 AKI 患者的肾脏疾病严重程度和远处器官功能障碍标志物有关。需要更大的研究来证实这些关系。
