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土耳其儿童中Toll样受体4和2基因多态性与慢性移植肾肾病的关联

Association between Toll-like receptors 4 and 2 gene polymorphisms with chronic allograft nephropathy in Turkish children.

作者信息

Mutlubas F, Mir S, Berdeli A, Ozkayin N, Sozeri B

机构信息

Department of Pediatric Nephrology, Faculty of Medicine, Ege University, Izmir, Turkey.

出版信息

Transplant Proc. 2009 Jun;41(5):1589-93. doi: 10.1016/j.transproceed.2009.02.079.

Abstract

Toll-like receptor (TLR) gene polymorphism is known to impair intracellular signaling pathways following adaptive immune responses. Our aim was to investigate the distribution of TLR4 and TLR2 gene polymorphisms among pediatric renal transplantation patients in relation to chronic allograft nephropathy (CAN). In addition to 115 healthy controls, we included 69 renal recipients, 19 of whom were identified as CAN by biopsy scored according to the Banff criteria. Polymorphisms at TLR4 Asp299Gly and/or Thr399Ile were present in 11.6% of renal transplant recipients. None of these subjects was identified in cosegregation with the Thr399Ile allele, whereas three had an isolated Asp299Gly and five had an isolated Thr399Ile. Neither renal recipients nor healthy controls were homozygous for both Asp299Gly and Thr399Ile polymorphisms. However, TLR4 Thr399Ile polymorphism and Ile allele was greater among CAN (-) versus CAN (+) recipients (P > .05). The frequency of TLR2 mutant type Gln allele was significantly higher in recipients than among healthy controls (P < .0001). However, the Gln allele frequency was similar between CAN (+) and CAN (-) patients. The results of present study may be speculated to show TLR4 and TLR2 gene polymorphisms as protective factors from CAN development due to impaired immune responses.

摘要

已知Toll样受体(TLR)基因多态性会损害适应性免疫反应后的细胞内信号通路。我们的目的是研究儿科肾移植患者中TLR4和TLR2基因多态性与慢性移植肾肾病(CAN)的关系。除了115名健康对照者外,我们纳入了69名肾移植受者,其中19名根据Banff标准经活检确定为CAN。肾移植受者中11.6%存在TLR4 Asp299Gly和/或Thr399Ile多态性。这些受试者中没有发现与Thr399Ile等位基因共分离的情况,而有3人存在孤立的Asp299Gly,5人存在孤立的Thr399Ile。肾移植受者和健康对照者均未同时为Asp299Gly和Thr399Ile多态性的纯合子。然而,CAN(-)受者中TLR4 Thr399Ile多态性和Ile等位基因的比例高于CAN(+)受者(P>.05)。受体中TLR2突变型Gln等位基因的频率显著高于健康对照者(P<.0001)。然而,CAN(+)和CAN(-)患者之间的Gln等位基因频率相似。本研究结果可能推测表明,TLR4和TLR2基因多态性是由于免疫反应受损而免受CAN发展影响的保护因素。

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