Gene Variant in Donors Affects Kidney Graft Survival
(HealthDay News) – A single nucleotide polymorphism (SNP) in the donor ABCB1 gene, known to alter protein expression, significantly increases the risk of long-term graft failure, according to a study published online Oct 11 in the Journal of the American Society of Nephrology.
Jason Moore, MD, of the Queen Elizabeth Hospital in Birmingham, UK, and colleagues conducted a study involving 4,471 white kidney-transplant recipients who had been treated with calcineurin inhibitors (CNIs). The authors sought to determine the impact of donor and recipient genotypes on clinical end points. Fifty-two SNPs across five genes were investigated.
In a discovery cohort of 811 patients, the researchers found that kidney donor CC genotype at C3435T within ABCB1 correlated with a significantly increased risk of long-term graft failure, compared with the non-CC genotype (hazard ratio [HR], 1.69). No other SNPs from donors or recipients correlated with graft survival or death. The association was validated in a cohort from Belfast involving 675 donors (HR, 1.68) and a cohort of 2,985 donors from the Collaborative Transplant Study (HR, 1.84).
"This study has identified an association between CC genotype of the functional C3435T polymorphism within ABCB1 of the transplant donor genome and worse long-term death-censored graft survival," the authors write. "Although this relationship may be context-specific, this ABCB1 gene variant represents an intuitive and attractive focus for future research efforts to evaluate the generalizability of these preliminary results."
One author disclosed being the recipient of an EFSD/Lilly Fellowship.