title: Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal Transplant Patients: A Validation Study.
abstract: Genome-wide association studies (GWAS) are designed to investigate single nucleotide polymorphisms (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.
authors.affiliation: Section of Nephrology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: H K
authors.initials: HK
authors.lastname: Pihlstrøm
authors.affiliation: Section of Nephrology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: G
authors.initials: G
authors.lastname: Mjøen
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, University Hospital Schleswig Holstein, Kiel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Mucha
authors.affiliation: K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Pathology, Oslo University Hospital, Oslo, Norway.
authors.forename: G
authors.initials: G
authors.lastname: Haraldsen
authors.affiliation: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, University Hospital Schleswig Holstein, Kiel, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Franke
authors.affiliation: British Heart Foundation, Glasgow Cardiovascular Research Centre, Glasgow, Scotland, UK.
authors.forename: A
authors.initials: A
authors.lastname: Jardine
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Fellström
authors.affiliation: Section of Nephrology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: H
authors.initials: H
authors.lastname: Holdaas
authors.affiliation: K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Norwegian PSC Research Center, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Research Institute of Internal Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.|Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Melum
mesh_terms: D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D055106:Genome-Wide Association Study; D005838:Genotype; D006084:Graft Rejection / Q000175:diagnosis* / Q000209:etiology; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
keywords: clinical research/practice; genetics; genomics; graft survival; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; molecular biology: single polynucleotide polymorphism