Singh Kamini, Prasad Kashi Nath, Mishra Priyanka, Singh Satyendra Kumar, Kharwar Nagendra Kumar, Prasad Narayan, Gupta Amit, Srivastava Janmejai Kumar
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India; Amity Institute of Biotechnology, Amity University, Lucknow, India.
Nephrology (Carlton). 2015 Jun;20(6):387-91. doi: 10.1111/nep.12398.
Cytokines play a critical role in the pathophysiology of end stage renal disease (ESRD). Tumour necrosis factor-a (TNF-α) is an important cytokine involved in initiation and progression of renal diseases. The present study evaluated the association of specific alleles/genotype of TNF-α with chronic renal failure (CRF) and ESRD.
A total of 30 CRF patients who were not on renal replacement therapy, 85 ESRD patients and 120 healthy controls were included in the study. The ESRD patients belonged to two subgroups: patients on peritoneal dialysis (PD) without peritonitis (n = 50) and with peritonitis (n = 35). TNF-α genotype (-308 G > A) was determined by polymerase chain reaction-restriction fragment length polymorphism. Level of TNF-α was detected in the sera of patients and healthy controls by enzyme linked immunosorbent assay (ELISA), and also in the dialysate of patients on PD.
The genotypic distributions of TNF-α (-308 G > A) were significantly different between patients and controls. Homozygous A/A genotype had significant association with CRF and ESRD (P < 0.001, odds ratio [OR] = 25.02). Frequency of homozygous A/A genotype was significantly higher in all subgroups of patients than controls (CRF 40% vs control 2.5%, P = 0.001; PD 54% vs control 2.5%, P < 0.001 and PD with peritonitis 62.8% vs control 2.5%, P < 0.001). Patients with homozygous A/A genotype had significantly elevated levels of TNF-α in the sera of patients and in the dialysate of PD patients.
Individuals with homozygous TNF-α (-308 G > A) polymorphisms has significant association with CRF and ESRD, and thus may be a predictor for development of the disease. Elevated TNF-α may be a contributory factor.
细胞因子在终末期肾病（ESRD）的病理生理学中起关键作用。肿瘤坏死因子-α（TNF-α）是一种参与肾脏疾病发生和发展的重要细胞因子。本研究评估了TNF-α的特定等位基因/基因型与慢性肾衰竭（CRF）和ESRD的关联。
本研究共纳入30例未接受肾脏替代治疗的CRF患者、85例ESRD患者和120例健康对照。ESRD患者分为两个亚组：未发生腹膜炎的腹膜透析（PD）患者（n = 50）和发生腹膜炎的PD患者（n = 35）。采用聚合酶链反应-限制性片段长度多态性方法测定TNF-α基因型（-308 G>A）。通过酶联免疫吸附测定（ELISA）检测患者和健康对照血清中的TNF-α水平，以及PD患者透析液中的TNF-α水平。
患者与对照之间TNF-α（-308 G>A）的基因型分布存在显著差异。纯合子A/A基因型与CRF和ESRD显著相关（P<0.001，比值比[OR]=25.02）。患者所有亚组中纯合子A/A基因型的频率均显著高于对照（CRF组40% vs对照组2.5%，P = 0.001；PD组54% vs对照组2.5%，P<0.001；发生腹膜炎的PD组62.8% vs对照组2.5%，P<0.001）。纯合子A/A基因型患者血清和PD患者透析液中的TNF-α水平显著升高。
具有纯合子TNF-α（-308 G>A）多态性的个体与CRF和ESRD显著相关，因此可能是疾病发生的预测指标。TNF-α升高可能是一个促成因素。
