Association between a single donor TARC/CCL17 promotor polymorphism and obstructive chronic lung allograft dysfunction after lung transplantation

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Abstract

Lung transplantation (LTx) outcome is hampered by development of chronic rejection, often manifested as the bronchiolitis obliterans syndrome (BOS). Low serum levels of thymus and activation-regulated chemokine (TARC/CCL17), a chemoattractant, measured during the first month post-LTx are predictive for BOS development. Since TARC/CCL17 promotor polymorphisms correlate with serum TARC/CCL17 levels, we investigated seven single-nucleotide polymorphisms (SNPs) within this region and their potential association with LTx outcome. We analyzed donor and patient SNP configurations and haplotypes and observed a trend between a donor SNP (rs223899) configuration and patient TARC/CCL17 serum levels post-LTx (p = 0.066). Interestingly, this SNP configuration in patients did not show any correlation with pre-LTx TARC/CCL17 serum levels (p = 0.776). Survival analysis showed that receiving a graft from a donor heterozygous for rs223899 has a disadvantageous impact on transplantation outcome. When stratified per donor SNP genotype, patients receiving a transplant from a heterozygous donor showed a lower BOS-free survival (p = 0.023) and survival rate (p = 0.0079). Since rs223899 is located within a NF?B binding site, heterozygosity at this position could result in a reduced TARC/CCL17 expression. Our data indicate that a single TARC/CCL17 promotor SNP in the donor correlates with lower serum TARC/CCL17 levels measured 1 month after LTx and affects clinical outcome after LTx.

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Budding, K., van Setten, J., van de Graaf, E. A., van Rossum, O. A., Kardol-Hoefnagel, T., Oudijk, E. J. D., … Otten, H. G. (2017). Association between a single donor TARC/CCL17 promotor polymorphism and obstructive chronic lung allograft dysfunction after lung transplantation. Frontiers in Immunology, 8(SEP). https://doi.org/10.3389/fimmu.2017.01109

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