Beta-Adrenergic Receptor Polymorphisms and Cardiac Graft Function in Potential Organ Donors AMERICAN JOURNAL OF TRANSPLANTATION Khush, K. K., Pawlikowska, L., Menza, R. L., Goldstein, B. A., Hayden, V., Nguyen, J., Kim, H., Poon, A., Sapru, A., Matthay, M. A., Kwok, P. Y., Young, W. L., Baxter-Lowe, L. A., Zaroff, J. G. 2012; 12 (12): 3377-3386

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.

View details for DOI 10.1111/j.1600-6143.2012.04266.x

View details for Web of Science ID 000311854800022

View details for PubMedID 22994654