title: Beta-adrenergic receptor polymorphisms and cardiac graft function in potential organ donors.
abstract: 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.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. kiran@stanford.edu
authors.forename: K K
authors.initials: KK
authors.lastname: Khush
authors.forename: L
authors.initials: L
authors.lastname: Pawlikowska
authors.forename: R L
authors.initials: RL
authors.lastname: Menza
authors.forename: B A
authors.initials: BA
authors.lastname: Goldstein
authors.forename: V
authors.initials: V
authors.lastname: Hayden
authors.forename: J
authors.initials: J
authors.lastname: Nguyen
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: A
authors.initials: A
authors.lastname: Poon
authors.forename: A
authors.initials: A
authors.lastname: Sapru
authors.forename: M A
authors.initials: MA
authors.lastname: Matthay
authors.forename: P Y
authors.initials: PY
authors.lastname: Kwok
authors.forename: W L
authors.initials: WL
authors.lastname: Young
authors.forename: L A
authors.initials: LA
authors.lastname: Baxter-Lowe
authors.forename: J G
authors.initials: JG
authors.lastname: Zaroff
mesh_terms: D000328:Adult; D001926:Brain Death; D005260:Female; D006085:Graft Survival / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D018342:Receptors, Adrenergic, beta-1 / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*; D012189:Retrospective Studies; D014019:Tissue Donors; D054928:Validation Studies as Topic; D018487:Ventricular Dysfunction, Left / Q000235:genetics*
chemical_list: D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2