Nuclear factor of activated T cell cytoplasmic 1 (NFATc1) insertion gene polymorphism as a possible trigger in acute T cell-mediated rejection (aTCMR) after kidney transplantation

IF 1.6 4区医学 Q4 IMMUNOLOGY

Transplant immunology Pub Date : 2024-10-24 DOI:10.1016/j.trim.2024.102139

Yisheng Ji , Congcong Chen , Pei Lu , Zijie Wang , Hao Chen , Li Sun , Shuang Fei , Xiaobing Ju , Ruoyun Tan , Min Gu

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Abstract

Background

To investigate the potential regulatory role of gene insertion or deletion (in/del) polymorphism in the occurrence of acute T cell-mediated rejection (aTCMR) after kidney transplantation.

Methods

We retrospectively analyzed the 5-year follow-up data of 133 recipients who underwent renal transplantation at the First Affiliated Hospital of Nanjing Medical University between February 1, 2010, and December 1, 2015. With target sequencing based on next-generation sequencing (NGS), tagger in/dels selection involved calculating the Hardy-Weinberg equilibrium (HWE), Minor Allele Frequency (MAF), and the linkage disequilibrium (LD) blocks. Significant in/dels associated with aTCMR were identified by intersecting the results obtained through analysis of covariance (ANCOVA) of clinical cofounders and model analysis in Rstudio using the “SNPassoc” package. Additionally, logistic models were employed to assess the associations between genotypes and the aTCMR occurrence in 5 years after surgery.

Results

NFATc1 rs55741427 insertion was identified to be significantly associated with the post-surgery aTCMR(OR = 2.66, P < 0.001). We constructed a conclusive model containing the occurrence of delayed graft function (DGF) and the insertion polymorphism of rs55741427, showing a favorable predictive ability (AUC = 0.766) for aTCMR after surgery. Based on the receiver operating characteristic (ROC) curve, all cases were stratified into aTCMR high-risk and low-risk groups. Kaplan-Meier curves for two groups revealed that the aTCMR high-risk group exhibited a more unfavorable graft survival outcome (P = 0.0048).

Conclusion

Insertion mutation of rs55741427 was found to be statistically correlated with the post-surgery aTCMR during 5 years of follow-up. Our model identified DGF and insertion of rs55741427 as two crucial aTCMR-related hazards, and aTCMR high-risk group showed a worse graft prognosis.

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活化 T 细胞胞浆核因子 1（NFATc1）插入基因多态性可能是肾移植后急性 T 细胞介导的排斥反应（aTCMR）的诱因。

背景：研究基因插入或缺失（in/del）多态性对肾移植后急性T细胞介导的排斥反应（aTCMR）发生的潜在调控作用：研究基因插入或缺失（in/del）多态性对肾移植术后急性T细胞介导的排斥反应（aTCMR）发生的潜在调控作用：我们回顾性分析了2010年2月1日至2015年12月1日期间在南京医科大学第一附属医院接受肾移植手术的133名受者的5年随访数据。通过基于下一代测序（NGS）的目标测序，计算哈代-温伯格平衡（HWE）、小等位基因频率（MAF）和连锁不平衡（LD）区块，从而选择标签in/dels。与 aTCMR 相关的重要 in/dels 是通过临床共因子协方差分析 (ANCOVA) 和使用 "SNPassoc "软件包在 Rstudio 中进行的模型分析得出的交叉结果确定的。此外，还采用了逻辑模型来评估基因型与术后 5 年内 aTCMR 发生率之间的关联：结果：发现 NFATc1 rs55741427 插入与术后 aTCMR 有显著相关性（OR = 2.66，P 结论：NFATc1 rs55741427 插入突变与术后 aTCMR 有显著相关性：研究发现，rs55741427的插入突变与手术后5年随访期间的aTCMR具有统计学相关性。我们的模型发现，DGF 和 rs55741427 插入突变是与 aTCMR 相关的两个关键危险因素，aTCMR 高危人群的移植物预后较差。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Transplant immunology 医学-免疫学

CiteScore

2.10

自引率

13.30%

发文量

198

审稿时长

48 days

期刊介绍： Transplant Immunology will publish up-to-date information on all aspects of the broad field it encompasses. The journal will be directed at (basic) scientists, tissue typers, transplant physicians and surgeons, and research and data on all immunological aspects of organ-, tissue- and (haematopoietic) stem cell transplantation are of potential interest to the readers of Transplant Immunology. Original papers, Review articles and Hypotheses will be considered for publication and submitted manuscripts will be rapidly peer-reviewed and published. They will be judged on the basis of scientific merit, originality, timeliness and quality.