白细胞介素-8、CXCR1、CXCR2 和选择素多态性与肾移植同种异体移植物结局的关系。

Association of polymorphisms of interleukin-8, CXCR1, CXCR2, and selectin with allograft outcomes in kidney transplantation.

机构信息

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea.

出版信息

Transplantation. 2011 Jan 15;91(1):57-64. doi: 10.1097/tp.0b013e3181fd0195.

DOI:10.1097/tp.0b013e3181fd0195

PMID:21452410

Abstract

BACKGROUND

Both chemokines and adhesion molecules mediate allograft rejection by recruiting leukocytes into the allograft. We investigated the association of six single nucleotide polymorphisms (SNPs) located in interleukin (IL)-8, CXCR1, CXCR2, and selectin with kidney allograft outcomes.

METHODS

The promoter regions of CXCR1 and CXCR2 were sequenced directly to find SNPs. Reporter gene assay was performed to determine the transcriptional activity of CXCR2 promoter polymorphisms. The association of SNPs in IL-8, CXCR1, CXCR2, and selectin with both acute rejection and estimated glomerular filtration rate at 1-year posttransplant was analyzed in 216 donor-recipient pairs of kidney transplantation.

RESULTS

The donor GA/AA genotypes of CXCR1 -2668G/A (rs2671222) were associated with increased risk for acute rejection even after adjusting for covariates such as gender, diabetes, preemptive transplantation, immunosuppressive regimen, relationship with the donor, and human leukocyte antigen mismatch (adjusted odds ratio 3.56; 95% confidence interval 1.37-9.27; P=0.009). Although the transcriptional activity of the CXCR2 variant promoter was 2.6-fold higher than that of the wild-type promoter (P=0.039), no significant association was observed between CXCR2 polymorphisms and kidney allograft outcomes. SNPs of IL-8, L-selectin, and E-selectin were not associated with kidney allograft outcomes.

CONCLUSION

The donor CXCR1 -2668 GA/AA genotypes were an independent risk factor for acute rejection in kidney transplantation.

摘要

背景

趋化因子和黏附分子通过将白细胞募集到移植物中来介导同种异体移植排斥反应。我们研究了位于白细胞介素（IL）-8、CXCR1、CXCR2 和选择素中的六个单核苷酸多态性（SNP）与肾移植结果的关联。

方法

直接对 CXCR1 和 CXCR2 的启动子区域进行测序以发现 SNP。进行报告基因检测以确定 CXCR2 启动子多态性的转录活性。在 216 对肾移植的供体-受者对中，分析了 IL-8、CXCR1、CXCR2 和选择素中的 SNP 与急性排斥反应以及移植后 1 年的估计肾小球滤过率的关联。

结果

即使在调整了性别、糖尿病、抢先移植、免疫抑制方案、与供体的关系和人类白细胞抗原错配等协变量后，CXCR1-2668G/A（rs2671222）的供体 GA/AA 基因型与急性排斥反应的风险增加相关（调整后的优势比 3.56；95%置信区间 1.37-9.27；P=0.009）。虽然 CXCR2 变体启动子的转录活性比野生型启动子高 2.6 倍（P=0.039），但 CXCR2 多态性与肾移植结果之间没有观察到显著关联。IL-8、L-选择素和 E-选择素的 SNP 与肾移植结果无关。