Basaal II - P50 - Association between a donor TARC/CCL17 promotor poly­mor­phism and impaired clinical outcome after lung transplantation

K. Budding, E.A. van de Graaf, J. van Setten, O.A. van Rossum, T. Kardol-Hoefnagel, E.-J.D. Oudijk, C.E. Hack, H.G. Otten

Chair(s): prof. dr. Eelco de Koning, LUMC

Thursday 10 march 2016

13:00 - 13:30h at Foyer

Categories: Postersessie

Parallel session: Postersessies XI - Opgesplitst in 3 tijdblokken en 3 categoriëen (klinisch, basaal, donatie)

Lung transplantation (LTx) outcome is hampered by development of chronic rejection, presented as the bronchiolitis obliterans syndrome (BOS). TARC/CCL17 is a chemo-attractant of which serum levels 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 selected single nucleotide polymorphisms (SNPs) present in this region and their potential association with LTx outcome. We analyzed donor and patient SNP configurations and haplotypes and identified a single SNP (rs223899) in the donor correlating with patient TARC/CCL17 serum levels (p=0.066) post-transplantation. 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 significant lower BOS-free survival (50% vs. 75%, p=0.023) and lower survival rate (50% vs 80%, p=0.0079). Since rs223899 is located within a NFκB binding site, heterozygosity at this position could result in a reduced expression of TARC/CCL17. Our data indicate that a single SNP in the promotor region of TARC/CCL17 correlates with lower serum TARC/CCL17 levels and affects clinical outcome after LTx.