Effect of adenosine monophosphate deaminase-1 C34T allele on the requirement for donor inotropic support and on the incidence of early graft dysfunction after cardiac transplantation.
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.
Taegtmeyer
Anne B
AB
Transplant Unit, Royal Brompton and Harefield NHS Trust, Harefield Hospital, Harefield, Middlesex, United Kingdom. a.taegtmeyer@imperial.ac.uk
Breen
Jane B
JB
Rogers
Paula
P
Johnson
Philip H
PH
Smith
John
J
Smolenski
Ryzard T
RT
Banner
Nicholas R
NR
Yacoub
Magdi H
MH
Barton
Paul J
PJ
D000659:AMP Deaminase / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D000740:Anemia / Q000150:complications; D001926:Brain Death; D002316:Cardiotonic Agents / Q000008:administration & dosage; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014019:Tissue Donors
D002316:Cardiotonic Agents; D000659:AMP Deaminase