Association Between a Single Donor Promotor Polymorphism and Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2017 Sep 22

PMID 28932229

Authors

Kevin Budding

Jessica van Setten

Eduard A van de Graaf

Oliver A van Rossum

Tineke Kardol-Hoefnagel

Erik-Jan D Oudijk

C Erik Hack

Henderikus G Otten

Affiliations

Soon will be listed here.

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 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 ( = 0.066). Interestingly, this SNP configuration in patients did not show any correlation with pre-LTx TARC/CCL17 serum levels ( = 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 ( = 0.023) and survival rate ( = 0.0079). Since rs223899 is located within a NFκB binding site, heterozygosity at this position could result in a reduced TARC/CCL17 expression. Our data indicate that a single 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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