Niknam Ahmad, Karimi Mohammad Hossein, Geramizadeh Bita, Roozbeh Jamshid, Yaghobi Ramin, Salehipour Mehdi
From the Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Exp Clin Transplant. 2017 Jun;15(3):295-305. doi: 10.6002/ect.2014.0253. Epub 2016 Dec 27.
Costimulatory molecules are important factors determining the outcome of transplant. The aim of the present study was to investigate the effect of CTLA-4, CD28, PD-1, and ICOS gene polymorphisms on the outcome of kidney transplant.
A total of 172 kidney transplant recipients were included in this study. There were 45 recipients (26%) who experienced acute rejection. The CTLA-4, PD-1, ICOS, and CD28 gene polymorphisms were evaluated by polymerase chain reaction and restriction fragment length polymorphism methods.
There were no differences between kidney transplant recipients with or without acute rejection in the distribution of genotypes and alleles of studied costimulatory molecules. Significant associations were observed between the AA genotype and the A allele of CTLA-4 1661 (P = .04, P = .05) and also CT and TT genotypes of PD-1.9 in the male compared with female subgroup of patients, with low frequency in the acute rejection group (P = .03; P = .04). Significant associations were observed between the AA genotype and the A allele of CTLA-4 -1661 (P = .02; P = .01) and also GA genotype of PD-1.3 (P = .03) in the male subgroup compared with female subgroup with low frequency of acute rejection. A significant association was observed between TC genotype of CD28 in the female compared with male subgroup of patients with high frequency of acute rejection (P = .05).
The above results suggest that genetic polymorphisms of costimulatory molecules function as sex-dependent risk factors for development of acute rejection. Further studies are needed in different populations.
共刺激分子是决定移植结果的重要因素。本研究旨在探讨CTLA-4、CD28、PD-1和ICOS基因多态性对肾移植结果的影响。
本研究共纳入172例肾移植受者。其中45例（26%）发生急性排斥反应。采用聚合酶链反应和限制性片段长度多态性方法评估CTLA-4、PD-1、ICOS和CD28基因多态性。
在发生或未发生急性排斥反应的肾移植受者中，所研究的共刺激分子的基因型和等位基因分布无差异。在男性患者与女性患者亚组中，观察到CTLA-4 1661的AA基因型和A等位基因（P = 0.04，P = 0.05）以及PD-1.9的CT和TT基因型之间存在显著关联，在急性排斥反应组中频率较低（P = 0.03；P = 0.04）。在男性亚组与女性亚组中，急性排斥反应频率较低时，观察到CTLA-4 -1661的AA基因型和A等位基因（P = 0.02；P = 0.01）以及PD-1.3的GA基因型（P = 0.03）之间存在显著关联。在急性排斥反应频率较高的女性患者与男性患者亚组中，观察到CD28的TC基因型之间存在显著关联（P = 0.05）。
上述结果表明，共刺激分子的基因多态性是急性排斥反应发生的性别依赖性危险因素。需要在不同人群中进行进一步研究。
