G1(T)
ASSOCIATION OF DONOR HEME OXYGENASE-1 (HO-1) GENE GT(N) REPEAT
POLYMORPHISM WITH DELAYED GRAFT FUNCTION (DGF) AND LONG TERM RENAL
ALLOGRAFT SURVIVAL
Moore, J1,2, Courtney, A3, Simmonds, M4, Hanvesakul, R2, Brand, O3, Briggs, D5, Ball, S2,
Cockwell, P 2, Maxwell, A3, Gough, S4, Borrows, R2
1
The Renal Unit, Wonford Hospital, Exeter, 2Department of Nephrology and Transplantation,
University Hospital Birmingham, 3Nephrology Research Group, Queen’s University of Belfast,
4
Oxford Centre for Diabetes, University of Oxford, 5National Blood Service, Birmingham
BACKGROUND: Heme oxygenase-1 (HO-1) may confer cytoprotection following kidney
transplantation. The functional HO-1 GT(n) repeat promoter polymorphism leads to higher expression
and activity when the GT(n) repeat length is short ([S], <25 GT repeats) compared with long ([L], ≥25
GT repeats), although previous studies (often underpowered) in transplantation have yielded conflicting
results.
STUDY AIM: To investigate whether donor HO-1 genotype influences kidney transplant outcomes.
METHODS:Genomic DNA was collected from a total of 1295 white kidney transplant donors from
two UK sites, Birmingham (n=601) and Belfast (n=694). The outcome measures of interest were
delayed graft function (DGF) and long term death-censored allograft loss.
RESULTS: In the Birmingham population, when compared with non-LL genotypes (i.e. SS and SL),
LL donors demonstrated a statistically significant association with DGF on both univariate and
multivariate logistic regression analysis (OR: 1.62; 95% CI 1.15-2.28, p=0.006). In addition, of those
patients with DGF, donor LL genotype was predictive of worse allograft survival (p=0.013). DGF data
was not available from the Belfast cohort. In the combined population over a 19.5 year time period,
graft survival was significantly worse with LL genotype donors in an adjusted Cox model (HR: 1.30;
95% CI 1.01-1.68, p=0.04).
CONCLUSION: To our knowledge, this is the largest study to date to investigate the relationship
between variation in the HO-1 promoter and kidney transplant outcomes. This “genetic biomarker” may
show utility in predicting the risk of DGF and allograft survival in individual patients and may prompt
future strategies to mitigate risk in this group.