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

Published

Journal Article

Prior studies have demonstrated associations between beta-adrenergic receptor (βAR) polymorphisms and left ventricular dysfunction-an important cause of allograft nonutilization for transplantation. We hypothesized that βAR 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 βAR single nucleotide polymorphisms were genotyped: β1AR 1165C/G (Arg389Gly), β1AR 145A/G (Ser49Gly), β2AR 46G/A (Gly16Arg) and β2AR 79C/G (Gln27Glu). In multivariable regression analyses, the β2AR46 SNP was significantly associated with LV systolic dysfunction, with each minor allele additively decreasing the odds for LV ejection fraction <50%. The β1AR1165 and β2AR46 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 μg/kg/min of dopamine compared to those with the CC and GG genotypes. However, no significant associations were found between βAR 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. βAR polymorphisms may be associated with cardiac dysfunction after brain death, but these relationships require further study in independent donor cohorts.

Full Text

Duke Authors

Cited Authors

  • Khush, KK; Pawlikowska, L; Menza, RL; Goldstein, BA; Hayden, V; Nguyen, J; Kim, H; Poon, A; Sapru, A; Matthay, MA; Kwok, PY; Young, WL; Baxter-Lowe, LA; Zaroff, JG

Published Date

  • December 2012

Published In

Volume / Issue

  • 12 / 12

Start / End Page

  • 3377 - 3386

PubMed ID

  • 22994654

Pubmed Central ID

  • 22994654

Electronic International Standard Serial Number (EISSN)

  • 1600-6143

International Standard Serial Number (ISSN)

  • 1600-6135

Digital Object Identifier (DOI)

  • 10.1111/j.1600-6143.2012.04266.x

Language

  • eng