Beta-adrenergic receptor polymorphisms and cardiac graft function in potential organ donors.

ABSTRACT: Prior studies have demonstrated associations between beta-adrenergic receptor (?AR) polymorphisms and left ventricular dysfunction-an important cause of allograft nonutilization for transplantation. We hypothesized that ?AR polymorphisms predispose donor hearts to LV dysfunction after brain death. A total of 1043 organ donors managed from 2001-2006 were initially studied. The following ?AR single nucleotide polymorphisms were genotyped: ?1AR 1165C/G (Arg389Gly), ?1AR 145A/G (Ser49Gly), ?2AR 46G/A (Gly16Arg) and ?2AR 79C/G (Gln27Glu). In multivariable regression analyses, the ?2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction <50%. The ?1AR1165 and ?2AR46 SNPs were associated with higher dopamine requirement during the donor management period: donors with the GG and AA genotypes had ORs of 2.64 (95% CI 1.52-4.57) and 2.70 (1.07-2.74) respectively for requiring >10 ?g/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between ?AR SNPs and cardiac dysfunction in 364 donors managed from 2007-2008, perhaps due to changes in donor management, lack of power in this validation cohort, or the absence of a true association. ?AR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts.

SUBMITTER: Khush KK 

PROVIDER: S-EPMC3513582 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature