The C34T T allele of the adenosine monophosphate deaminase-1 (AMPD1) gene has been
associated with improved outcome in patients with cardiac dysfunction. We hypothesized
that possession of this allele by donor hearts plays a role in the outcome of cardiac
transplantation; 262 cardiac donors and 190 of their recipients were studied. AMPD1
C34T genotype was determined using 5' exonuclease chemistry. Requirement for inotropic
agents before organ donation, 1-year post-transplantation survival, cause of death,
and factors known to affect survival after transplantation were also studied. Multiple
regression models for factors affecting survival were constructed. A significant yearly
increase in frequency of the T allele in donors was noted (0.06 to 0.18 from 1994
to 1999). Donors with the CT or TT genotype required less inotropic support than those
with the CC genotype (mean number of inotropes per donor with CT or TT genotype 0.27
compared with 0.47 per donor with CC genotype, n = 206, p = 0.03). Recipients of T-allele-carrying
organs showed worse 1-year survival after transplantation (59% vs 79%, p <0.001).
Excess deaths in these patients was due to early graft dysfunction (odds ratio for
early graft dysfunction 6.6, 95% confidence interval 2 to 21.6, p = 0.0001). Multivariate
analysis showed donor AMPD1 genotype, recipient age, and pretransplantation anemia
to independently affect 1-year post-transplantation survival (adjusted hazard ratios
3.7, 1.06, and 2.6, respectively). In conclusion, possession of the AMPD1 T allele
is associated with decreased inotropic requirements before heart donation. The incidence
of early graft dysfunction, however, was significantly higher in recipients who received
AMPD1 T-allele-possessing organs resulting in worse 1-year survival.