AGT 单倍型与心脏移植患者抗体介导的排斥反应有关。
AGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients.
机构信息
Grupo de Investigación en Cardiología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), A Coruña, Spain.
Servicio de Cardiología, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC)-CIBERCV, Sergas Universidade da Coruña (UDC), A Coruña, Spain.
出版信息
PLoS One. 2019 Jul 23;14(7):e0219345. doi: 10.1371/journal.pone.0219345. eCollection 2019.
INTRODUCTION
One of the main problems involved in heart transplantation (HT) is antibody-mediated rejection (AMR). Many aspects of AMR are still unresolved, including its etiology, diagnosis and treatment. In this project, we hypothesize that variants in genes involved in B-cell biology in HT patients can yield diagnostic and prognostic information about AMR.
METHODS
Genetic variants in 61 genes related to B-cell biology were analyzed by next generation sequencing in 46 HT patients, 23 with and 23 without AMR.
RESULTS
We identified 3 single nucleotide polymorphisms in ITGA4 gene (c.1845G>A, c.2633A>G, and c.2883C>T) that conformed the haplotype AGT-ITGA4. This haplotype is associated with the development of AMR. Moreover, AMR patients with the haplotype AGT-ITGA4 present lower levels of integrin α-4 in serum samples compared to the reference GAC haplotype in control patients.
CONCLUSION
We can conclude that polymorphisms in genes related to the biology of B-cells could have an important role in the development of AMR. In fact, the AGT haplotype in ITGA4 gene could potentially increase the risk of AMR.
简介
心脏移植（HT）中涉及的主要问题之一是抗体介导的排斥反应（AMR）。AMR 的许多方面仍未得到解决，包括其病因、诊断和治疗。在这个项目中，我们假设 HT 患者中涉及 B 细胞生物学的基因变异可以为 AMR 提供诊断和预后信息。
方法
通过下一代测序分析了 46 名 HT 患者（23 名有 AMR，23 名无 AMR）中 61 个与 B 细胞生物学相关的基因中的遗传变异。
结果
我们在 ITGA4 基因中发现了 3 个单核苷酸多态性（c.1845G>A、c.2633A>G 和 c.2883C>T），这些多态性构成了 AGT-ITGA4 单倍型。该单倍型与 AMR 的发生有关。此外，与对照患者中的参考 GAC 单倍型相比，携带 AGT-ITGA4 单倍型的 AMR 患者的血清样本中整合素 α-4 水平较低。
结论
我们可以得出结论，与 B 细胞生物学相关的基因中的多态性可能在 AMR 的发展中起重要作用。事实上，ITGA4 基因中的 AGT 单倍型可能会增加 AMR 的风险。
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