BACKGROUND: We examined, through genome-wide association studies (GWAS), the correlation between recipient genetic variation and renal function at five yr. METHODS: Our cohort contained 326 Irish, first time, kidney-only, deceased donor, transplant recipients on calcineurin inhibitors (263 had a functioning graft at five yr) between 1993 and 2002. Outcomes were creatinine at five yr and long-term graft function. RESULTS: Two variants were identified showing borderline genome-wide significance - one on chromosome 18 (p = 4.048e-08, rs6565887) and another on chromosome 14 (p = 7.631e-08, rs3811321). Individually, the two SNPs explained up to 8.8% and 11.29% of five-yr creatinine variance, respectively, while together they explained up to 17.4% of trait variance. Both variants were predictors of long-term allograft function (p = 0.004, 70% vs 30% survival at 10 yr). The chromosome 14 variant is located in the intergenic region of the T-Cell Receptor Alpha locus. CONCLUSIONS: Using a genome-wide approach, we have identified two associations with five-yr creatinine levels in renal transplant recipients treated with calcineurin inhibitors. Independent replication is now warranted to clarify the clinical significance of these results.
BACKGROUND: We examined, through genome-wide association studies (GWAS), the correlation between recipient genetic variation and renal function at five yr. METHODS: Our cohort contained 326 Irish, first time, kidney-only, deceased donor, transplant recipients on calcineurin inhibitors (263 had a functioning graft at five yr) between 1993 and 2002. Outcomes were creatinine at five yr and long-term graft function. RESULTS: Two variants were identified showing borderline genome-wide significance - one on chromosome 18 (p = 4.048e-08, rs6565887) and another on chromosome 14 (p = 7.631e-08, rs3811321). Individually, the two SNPs explained up to 8.8% and 11.29% of five-yr creatinine variance, respectively, while together they explained up to 17.4% of trait variance. Both variants were predictors of long-term allograft function (p = 0.004, 70% vs 30% survival at 10 yr). The chromosome 14 variant is located in the intergenic region of the T-Cell Receptor Alpha locus. CONCLUSIONS: Using a genome-wide approach, we have identified two associations with five-yr creatinine levels in renal transplant recipients treated with calcineurin inhibitors. Independent replication is now warranted to clarify the clinical significance of these results.
Authors: Caragh P Stapleton; Andreas Heinzel; Weihua Guan; Peter J van der Most; Jessica van Setten; Graham M Lord; Brendan J Keating; Ajay K Israni; Martin H de Borst; Stephan J L Bakker; Harold Snieder; Michael E Weale; Florence Delaney; Maria P Hernandez-Fuentes; Roman Reindl-Schwaighofer; Rainer Oberbauer; Pamala A Jacobson; Patrick B Mark; Fiona A Chapman; Paul J Phelan; Claire Kennedy; Donal Sexton; Susan Murray; Alan Jardine; Jamie P Traynor; Amy Jayne McKnight; Alexander P Maxwell; Laura J Smyth; William S Oetting; Arthur J Matas; Roslyn B Mannon; David P Schladt; David N Iklé; Gianpiero L Cavalleri; Peter J Conlon Journal: Am J Transplant Date: 2019-03-28 Impact factor: 8.086
Authors: Nicholas J Steers; Yifu Li; Zahida Drace; Justin A D'Addario; Clara Fischman; Lili Liu; Katherine Xu; Young-Ji Na; Y Dana Neugut; Jun Y Zhang; Roel Sterken; Olivia Balderes; Drew Bradbury; Nilgun Ozturk; Fatih Ozay; Sanya Goswami; Karla Mehl; Jaclyn Wold; Fatima Z Jelloul; Mersedeh Rohanizadegan; Christopher E Gillies; Elena-Rodica M Vasilescu; George Vlad; Yi-An Ko; Sumit Mohan; Jai Radhakrishnan; David J Cohen; Lloyd E Ratner; Francesco Scolari; Katalin Susztak; Matthew G Sampson; Silvia Deaglio; Yasar Caliskan; Jonathan Barasch; Aisling E Courtney; Alexander P Maxwell; Amy J McKnight; Iuliana Ionita-Laza; Stephan J L Bakker; Harold Snieder; Martin H de Borst; Vivette D'Agati; Antonio Amoroso; Ali G Gharavi; Krzysztof Kiryluk Journal: N Engl J Med Date: 2019-05-16 Impact factor: 91.245
Authors: Caragh P Stapleton; Kelly A Birdwell; Amy Jayne McKnight; Alexander P Maxwell; Patrick B Mark; M Lee Sanders; Fiona A Chapman; Jessica van Setten; Paul J Phelan; Claire Kennedy; Alan Jardine; Jamie P Traynor; Brendan Keating; Peter J Conlon; Gianpiero L Cavalleri Journal: Am J Transplant Date: 2018-09-05 Impact factor: 8.086
Authors: Benjamin Vincent; Adam Buntzman; Benjamin Hopson; Chris McEwen; Lindsay Cowell; Ali Akoglu; Helen Zhang; Jeffrey Frelinger Journal: Cell Immunol Date: 2015-11-02 Impact factor: 4.868