AGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients
Nuñez Fernandez, Lucia; Marron Liñares, Grecia; Crespo Leiro, Marisa; Barge Caballero, Eduardo; Alvarez López, Eloy; Suárez Fuentetaja, Natalia; Paniagua Martín, María Jesús; Pombo Otero, Jorge; Muñiz García, Javier; Tan, Carmela D; Rodriguez, E Rene; Vázquez Rodríguez, José Manuel; Hermida Prieto, Manuel
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Identificadores
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Fecha de publicación
2019Título de revista
PLoS One
Tipo de contenido
Artigo
DeCS
integrinas | secuenciación de nucleótidos de alto rendimiento | trasplante de corazón | mediana edad | humanos | haplotipos | anticuerpos | rechazo del injerto | simulación por ordenador | predisposición genética a la enfermedadMeSH
Integrins | Middle Aged | Humans | Antibodies | Haplotypes | Heart Transplantation | Computer Simulation | High-Throughput Nucleotide Sequencing | Genetic Predisposition to Disease | Graft RejectionResumen
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 alpha-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.
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