Single nucleotide polymorphisms and long term clinical outcome in renal transplant patients. A validation study.

Hege K Pihlstrøm, Geir Mjøen, Sören Mucha, Guttorm Haraldsen, Andre Franke, Alan Jardine, Bengt Fellström, Hallvard Holdaas, Espen Melum
Year of publication:
Journal title abbreviated:
Am. J. Transplant.
Journal title long:
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Impact factor:
Genome-wide association studies (GWAS) are designed to investigate single nucleotide polymorphisms (SNP) and the association to a clinical phenotype. A previous GWAS performed in 300 renal transplant recipients identified two SNPs (rs3811321 and rs6565887) associated with creatinine and clinical outcome. We sought to validate these findings. Genotyping of the two SNPs were performed using Taqman assays in 1638 Caucasians participating in the ALERT-study. Primary endpoint was death-censored graft loss, and secondary endpoint was all-cause mortality. Applying Cox regression, no crude association to graft loss was found for rs3811321 on chromosome 14 (HR 0.87, 95% CI 0.59-1.29, p=0.50) or rs6565887 on chromosome 18 (HR 0.88, CI 0.62-1.25, p=0.48). Multivariable adjustments did not change results, nor did evaluation of the number of risk alleles formed by the two SNPs. No association with mortality was detected. In conclusion, an impact of two SNPs on chromosomes 14 and 18 on death censored graft survival or all-cause mortality was not confirmed. Our results emphasize the importance of validating findings from high-throughput genetics studies and call for large collaborative research initiatives in the field of transplantation outcomes. This article is protected by copyright. All rights reserved.