供者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。

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

机构信息

Department of Nephrology and Renal Transplantation, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

Department Of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.

出版信息

Clin Transplant. 2024 Oct;38(10):e15475. doi: 10.1111/ctr.15475.

DOI:10.1111/ctr.15475

PMID:39412439

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.

摘要

背景

受体的 VEGF-A 多态性已被报道与急性同种异体排斥反应的风险相关。然而，供体的 VEGF-A 基因多态性与排斥反应之间的关系至今仍未阐明。

方法

本研究分析了 160 名接受肾移植的供体和受者（排斥者，n=80；非排斥者，n=80）中 9 个位点的 VEGF-A 基因 SNPs。通过 RT-PCR、ELISA 和免疫组织化学分别分析血 VEGF-A mRNA、血浆 VEGF 水平和移植肾内 VEGF 表达。

结果

在供体与排斥者之间比较时，VEGF-634 C>G 多态性基因型[GG 基因型，p<0.0001；比值比（95%可信区间）=17.74（5.16-60.96）]；VEGF-1154 G>A [AG 基因型，p<0.0001，比值比（95%可信区间）=16.07（3.68-70.15）]；VEGF+936 C>T [CT 基因型，p<0.0001，比值比（95%可信区间）=178.64（23.28-1370.9），TT 基因型，p<0.0001；比值比（95%可信区间）=3149（278.91-35553）]；VEGF-1455 T>C [CC 基因型，p 值=0.0464，比值比（95%可信区间）=3.13（1.07-9.10）]；VEGF-2578 C>A [CA 基因型，p=0.0426，比值比（95%可信区间）=4.62（1.03-20.59），AA 基因型，p 值<0.0001，比值比（95%可信区间）=21.89（4.94-97.04）]；VEGF-2549 18 bp 插入/缺失[ID 基因型，p 值<0.0001，比值比（95%可信区间）=27.27（3.61-205.73）和 DD 基因型，p 值<0.0001，比值比（95%可信区间）=25.18（3.30-191.89）]与急性排斥反应风险显著相关。在排斥者与非排斥者之间比较时，VEGF-1190 G>A 的 GA 基因型和 VEGF-1455 T>C 的 TC 基因型与排斥反应的风险相关。在比较排斥者与非排斥者的供体 VEGF 时，VEGF-634 C>G 的 CG 基因型、VEGF-1154 G>A 的 AG 基因型；VEGF-1190 G>A 的 GA 基因型与排斥反应相关。排斥者组的血 VEGF-A mRNA 和血浆 VEGF 水平高于非排斥者组。