Open AccessAGT haplotype in ITGA4 gene is related to antibody-mediated rejection in heart transplant patients
Author(s) -
Lucı́a Núñez,
Grecia M Marrón-Liñares,
María G. Crespo-Leiro,
Eduardo BargeCaballero,
Eloy Álvarez-López,
Natalia Suárez-Fuentetaja,
María J. PaniaguaMartin,
Jorge Reynolds Pombo,
Javier Muñiz,
Carmela D. Tan,
E. René Rodríguez,
José Manuel VázquezRodríguez,
Manuel Hermida-Prieto
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0219345
Subject(s) - haplotype , gene , biology , transplantation , single nucleotide polymorphism , genetics , immunology , medicine , allele , genotype
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.