Single-nucleotide polymorphisms in the β-adrenergic receptor genes are associated with lung allograft utilization.
BACKGROUND
Pulmonary edema and associated impaired oxygenation are a major reason for rejection of donor lung allografts offered for transplantation. Clearance of pulmonary edema can be upregulated by stimulation of β-adrenergic receptors (βARs). Single-nucleotide polymorphisms (SNPs) in βAR genes have functional effects in vitro and in vivo. We hypothesized that SNPs in βAR genes would be associated with rates of utilization of donor lung allografts offered for transplantation.


METHODS
Nine hundred fifty-one organ donors were genotyped for 4 amino-acid-coding SNPs in the βAR genes. Lung allograft utilization was compared among donors stratified by genotypes.


RESULTS
Utilization of donor lung allografts was 55% vs 35% (p = 0.02) among donors with GG vs AA/AG genotypes of the Ser49Gly SNP, 39% vs 32% (p = 0.04) with GG vs AA/AG genotype of Gly16Arg SNP and 37% vs 32% (p = 0.1) with CC vs GC/GG genotype of the Arg389Gly SNP. In the combined analysis, donors carrying 0 or 1 associated genotype had a utilization rate of 33%, whereas donors carrying 2 or 3 associated genotypes had utilization rates of 44% and 58%, respectively (p = 0.008). There was a stepwise decrease in chest radiograph infiltrates and an increase in partial pressure of oxygen/fraction of inspired oxygen (PaO(2)/FIO(2)) with an increasing number of these associated genotypes.


CONCLUSIONS
Genetic variants in the βAR genes among organ donors are associated with higher rates of lung allograft utilization. The increased utilization may be related to increased clearance of pulmonary edema and improved oxygenation in donors with favorable genotypes and suggests that βAR agonists may have a role in donor management.
Sapru
Anil
A
Department of Pediatrics, Cardiovascular Research Institute, University of California San Francisco, San Franscisco, California 94143, USA. anil.sapru@ucsf.edu
Pawlikowska
Ludmila
L
Liu
Kathleen D
KD
Khush
Kiran K
KK
Ann-Baxter-Lowe
Lee
L
Hayden
Vanessa
V
Menza
Rebecca L
RL
Convery
Maureen
M
Poon
Annie
A
Landeck
Megan
M
Zaroff
Jonathan G
JG
Matthay
Michael A
MA
D000328:Adult; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D016040:Lung Transplantation / Q000592:standards*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011654:Pulmonary Edema / Q000503:physiopathology; D011943:Receptors, Adrenergic, beta / Q000235:genetics* / Q000502:physiology; D012189:Retrospective Studies; D009927:Tissue and Organ Procurement / Q000379:methods / Q000706:statistics & numerical data*; D014184:Transplantation, Homologous
D011943:Receptors, Adrenergic, beta