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CD28、CD86、CTLA-4 和 PD-1 基因多态性对埃及受者急性肾移植排斥反应和移植物存活的影响。

Impact of CD 28, CD86, CTLA-4 and PD-1 genes polymorphisms on acute renal allograft rejection and graft survival among Egyptian recipients.

机构信息

Nephrology and Transplant Unit, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

Center of Excellence for Genome and Cancer Research, Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.

出版信息

Sci Rep. 2024 Jan 24;14(1):2047. doi: 10.1038/s41598-024-52195-0.

Abstract

To study the impact of four gene polymorphisms on acute renal allograft rejection (AR) and graft survival among Egyptian population. These 4 gene polymorphisms include: (1) CD 28 (rs3116496), (2) CD86 (rs1129055), (3) CTLA-4 (rs3087243), (4) PD-1 (rs2227982). This is a non-concurrent cohort study including 50 kidney transplant recipients diagnosed histopathologically as (AR) [study group] and another 50 matched allograft recipients without AR [control group]. Blood samples were taken from both groups and subjected to genotyping for the selected four genetic polymorphisms by TaqMan genotyping assay. The difference in genotypic distribution of CD 28: rs3116496 and CD86: rs1129055 wasn't statistically significant between the study and control groups (P = 0.22 and 0.33 respectively) and also both polymorphisms had no effect on graft survival (P = 0.36 and 0.74 respectively) while the addition of C allele to IVS3 +17T/C polymorphism in CD28 gene showed a protective effect against AR (P = 0.03). CTLA-4: rs3087243 AG genotype showed a protective effect against AR as it was more frequent in no rejection group compared to those with AR (P = 0.001) with a statistically significant impact on graft survival (P < 0.001), while PD-1: rs2227982 AG genotype was equally distributed between both groups (variant of unknown significance). There was no detected association between CD86 polymorphism: rs1129055 and CD 28 polymorphism: rs3116496 with the development of AR. However, C allele of CD 28 IVS3 +17T/C polymorphism and CTLA-4 polymorphism: rs3087243AG genotype both demonstrated a protective effect against AR.

摘要

研究四种基因多态性对埃及人群急性肾移植排斥(AR)和移植物存活的影响。这四种基因多态性包括:(1)CD28(rs3116496),(2)CD86(rs1129055),(3)CTLA-4(rs3087243),(4)PD-1(rs2227982)。这是一项非同期队列研究,包括 50 例经组织病理学诊断为 AR 的肾移植受者(研究组)和另外 50 例无 AR 的匹配同种异体受者(对照组)。从两组采集血样,采用 TaqMan 基因分型法对选定的四种遗传多态性进行基因分型。研究组和对照组之间 CD28:rs3116496 和 CD86:rs1129055 的基因型分布差异无统计学意义(分别为 P=0.22 和 0.33),且两种多态性均对移植物存活无影响(分别为 P=0.36 和 0.74),而 CD28 基因 IVS3+17T/C 多态性的 C 等位基因增加则显示出对 AR 的保护作用(P=0.03)。CTLA-4:rs3087243AG 基因型对 AR 有保护作用,因为在无排斥组中比在 AR 组中更常见(P=0.001),对移植物存活有统计学意义(P<0.001),而 PD-1:rs2227982AG 基因型在两组之间分布均等(意义不明的变异)。未发现 CD86 多态性:rs1129055 与 CD28 多态性:rs3116496 与 AR 的发展有关。然而,CD28 IVS3+17T/C 多态性的 C 等位基因和 CTLA-4 多态性:rs3087243AG 基因型均显示出对 AR 的保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/11c8/10808544/0ec79aebfdd0/41598_2024_52195_Fig1_HTML.jpg

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