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Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal Transplant Patients: A Validation Study
Natl Hosp Norway, Oslo Univ Hosp, Nephrol Sect, Dept Transplantat Med,Div Surg Inflammatory Med &, Oslo, Norway..
Natl Hosp Norway, Oslo Univ Hosp, Nephrol Sect, Dept Transplantat Med,Div Surg Inflammatory Med &, Oslo, Norway..
Christian Albrechts Univ Kiel, Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, Kiel, Germany..
Univ Oslo, Inst Clin Med, KG Jebsen Inflammat Res Ctr, Oslo, Norway.;Oslo Univ Hosp, Dept Pathol, Oslo, Norway..
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2017 (English)In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 17, no 2, p. 528-533Article in journal (Refereed) Published
Abstract [en]

Genome-wide association studies (GWAS) are designed to investigate single nucleotide polymor-phisms (SNPs) and the association with a clinical phenotype. A previous GWAS performed in 300 renal transplant recipients identified two SNPs (rs3811321 and rs6565887) associated with serum creatinine and clinical outcome. We sought to validate these findings. Genotyping of the two SNPs was performed using Taqman assays in 1638 Caucasians participating in the Assessment of LEscol in Renal Transplant (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 (hazard ratio [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.

Place, publisher, year, edition, pages
WILEY , 2017. Vol. 17, no 2, p. 528-533
National Category
Surgery
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URN: urn:nbn:se:uu:diva-320695DOI: 10.1111/ajt.13995ISI: 000397418300027PubMedID: 27483393OAI: oai:DiVA.org:uu-320695DiVA, id: diva2:1090531
Available from: 2017-04-24 Created: 2017-04-24 Last updated: 2017-04-24Bibliographically approved

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