Association of Donor Vascular Endothelial Growth Factor Gene Polymorphism With Acute Renal Allograft Rejection

IF 1.9 4区医学 Q2 SURGERY

Clinical Transplantation Pub Date : 2024-10-16 DOI:10.1111/ctr.15475

Narayan Prasad, Brijesh Yadav, Mansi Bhatt, Ranjeet Chauhan, Vinita Agrawal

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引用次数: 0

Abstract

Background

Recipient's VEGF-A polymorphisms have been reported to be associated with the risk of acute allograft rejection. However, an association of the donor's VEGF-A gene polymorphism with rejection remained unelucidated till now.

Methods

In this study, VEGF-A gene SNPs at nine loci were analyzed in 160 kidney donors and recipients with rejection (rejectors, n = 80) and without rejection (non-rejectors, n = 80). Blood VEGF-A mRNA, plasma VEGF level, and intragraft VEGF expression were also analyzed by RT-PCR, ELISA, and immunohistochemistry, respectively.

Results

On comparing between the donor and rejectors, the polymorphic genotypes of VEGF –634 C>G [GG genotype, p < 0.0001; OR (95% CI) = 17.74 (5.16–60.96)]; VEGF –1154 G>A [AG genotype, p < 0.0001, OR (95% CI) = 16.07 (3.68–70.15)]; VEGF +936 C>T [CT genotype, p < 0.0001, OR (95% CI) = 178.64 (23.28–1370.9), and TT genotype, p < 0.0001; OR (95% CI) = 3149 (278.91–35 553)]; VEGF –1455 T>C [CC genotype, p value = 0.0464, OR (95% CI) = 3.13 (1.07–9.10)]; VEGF –2578 C>A [CA genotype, p = 0.0426, OR (95% CI) = 4.62 (1.03–20.59), and AA genotype, p value < 0.0001, OR (95% CI) = 21.89 (4.94–97.04)]; VEGF –2549 18 bp Insertion/Deletion [ID genotype, p value < 0.0001, OR (95% CI) = 27.27 (3.61–205.73) and DD genotype, p value < 0.0001, OR (95% CI) = 25.18 (3.30–191.89) were significantly associated with acute rejection risk. On comparing rejectors versus non-rejectors, GA genotype of VEGF –1190 G>A and TC genotype of VEGF –1455 T>C were associated with the risk of rejection. On comparing donor VEGF between rejectors and non-rejectors, CG genotype of VEGF –634 C>G, AG of VEGF –1154 G>A; GA of VEGF –1190 G>A were associated with rejection. The blood VEGF-A mRNA and plasma VEGF levels were higher in the rejectors group compared to non-rejectors.

Conclusions

Besides the recipient's VEGF SNPS, the donor's VEGF SNPs are also associated with the risk of acute rejection and may be closely monitored in evaluation to determine the risk of rejection.

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供体血管内皮生长因子基因多态性与急性肾移植排斥反应的关系

背景据报道，受者的血管内皮生长因子-A基因多态性与急性同种异体移植排斥反应的风险有关。然而，供体的 VEGF-A 基因多态性与排斥反应的关系至今仍未阐明。方法在这项研究中，分析了160名肾脏供体和受体中存在排斥反应（排斥反应者，80人）和不存在排斥反应（非排斥反应者，80人）的9个位点的VEGF-A基因SNPs。此外，还分别通过 RT-PCR、ELISA 和免疫组化方法分析了血液 VEGF-A mRNA、血浆 VEGF 水平和移植物内 VEGF 表达。结果在供体和排斥者之间进行比较，VEGF -634 C>G [GG 基因型，p < 0.0001; OR (95% CI) = 17.74 (5.16-60.96)]; VEGF -1154 G>A [AG 基因型，p < 0.0001, OR (95% CI) = 16.07 (3.68-70.15)]; VEGF +936 C>T [CT 基因型，p < 0.0001, OR (95% CI) = 178.64 (23.28-1370.9), and TT 基因型，p < 0.0001; OR (95% CI) = 3149 (278.91-35 553)]; VEGF -1455 T>C [CC 基因型，p 值 = 0.0464, OR (95% CI) = 3.13 (1.07-9.10)]; VEGF -2578 C>A [CA 基因型，p = 0.0426, OR (95% CI) = 4.62 (1.03-20.59), AA 基因型，p 值 < 0.0001, OR (95% CI) = 21.89 (4.94-97. 04)]; VEGF -2578 T>C [VEGF -1455 T>C 基因型，p 值 = 0.04）]；VEGF -2549 18 bp插入/缺失[ID基因型，p值为< 0.0001，OR（95% CI）= 27.27（3.61-205.73）和DD基因型，p值为< 0.0001，OR（95% CI）= 25.18（3.30-191.89）]与急性排斥风险显著相关。比较排斥者与非排斥者，VEGF -1190 G>A 的 GA 基因型和 VEGF -1455 T>C 的 TC 基因型与排斥风险有关。比较排斥反应者和非排斥反应者的供体 VEGF，VEGF -634 C>G 的 CG 基因型、VEGF -1154 G>A 的 AG 基因型和 VEGF -1190 G>A 的 GA 基因型与排斥反应有关。与非排斥反应组相比，排斥反应组的血液 VEGF-A mRNA 和血浆 VEGF 水平更高。结论除受者的血管内皮生长因子 SNPS 外，供体的血管内皮生长因子 SNPS 也与急性排斥反应的风险有关，因此在评估确定排斥反应风险时应密切监测。

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

Clinical Transplantation 医学-外科

CiteScore

3.70

自引率

4.80%

发文量

286

审稿时长

2 months

期刊介绍： Clinical Transplantation: The Journal of Clinical and Translational Research aims to serve as a channel of rapid communication for all those involved in the care of patients who require, or have had, organ or tissue transplants, including: kidney, intestine, liver, pancreas, islets, heart, heart valves, lung, bone marrow, cornea, skin, bone, and cartilage, viable or stored. Published monthly, Clinical Transplantation’s scope is focused on the complete spectrum of present transplant therapies, as well as also those that are experimental or may become possible in future. Topics include: Immunology and immunosuppression; Patient preparation; Social, ethical, and psychological issues; Complications, short- and long-term results; Artificial organs; Donation and preservation of organ and tissue; Translational studies; Advances in tissue typing; Updates on transplant pathology;. Clinical and translational studies are particularly welcome, as well as focused reviews. Full-length papers and short communications are invited. Clinical reviews are encouraged, as well as seminal papers in basic science which might lead to immediate clinical application. Prominence is regularly given to the results of cooperative surveys conducted by the organ and tissue transplant registries. Clinical Transplantation: The Journal of Clinical and Translational Research is essential reading for clinicians and researchers in the diverse field of transplantation: surgeons; clinical immunologists; cryobiologists; hematologists; gastroenterologists; hepatologists; pulmonologists; nephrologists; cardiologists; and endocrinologists. It will also be of interest to sociologists, psychologists, research workers, and to all health professionals whose combined efforts will improve the prognosis of transplant recipients.