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A genome‐wide association study of recipient genotype and medium‐term kidney allograft function
Author(s) -
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.
Publication year - 2013
Publication title -
clinical transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 76
eISSN - 1399-0012
pISSN - 0902-0063
DOI - 10.1111/ctr.12093
Subject(s) - genome wide association study , medicine , calcineurin , renal function , creatinine , kidney transplantation , chromosome , genotype , locus (genetics) , snp , transplantation , genetics , oncology , single nucleotide polymorphism , biology , gene
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 I rish, 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 SNP s 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 ‐ C ell R eceptor A lpha 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.