A genome‐wide association study of recipient genotype and medium‐term kidney allograft function. (21st February 2013)

• Record Type: Journal Article
• Authors: O'Brien, Robert P.; Phelan, Paul J.; Conroy, Judith; O'Kelly, Patrick; Green, Andrew; Keogan, Mary; O'Neill, Derek; Jennings, Susan; Traynor, Carol; Casey, Jillian; McCormack, Mark; Conroy, Ronan; Chubb, Anthony; Ennis, Sean; Shields, Denis C.; Cavalleri, Gianpiero L.; Conlon, Peter J.
• Is Part Of: Clinical transplantation. Volume 27:Number 3(2013:May/Jun.)
• Page Start: 379
• Page End: 387
• Publication Date: 2013-02-21
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ctr.12093
• Languages: English
• ISSNs: 0902-0063

Abstract

<abstract abstract-type="main" id="ctr12093-abs-0001"> <title>Abstract</title> <sec id="ctr12093-sec-0001" sec-type="section"> <title>Background</title> <p>We examined, through genome‐wide association studies (GWAS), the correlation between recipient genetic variation and renal function at five yr.</p> </sec> <sec id="ctr12093-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="ctr12093-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="ctr12093-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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.</p> </sec> </abstract>