Kiran Kaur Khush, MD

Publication Details

  • Single-nucleotide polymorphisms in the beta-adrenergic receptor genes are associated with lung allograft utilization JOURNAL OF HEART AND LUNG TRANSPLANTATION Sapru, A., Pawlikowska, L., Liu, K. D., Khush, K. K., Ann-Baxter-Lowe, L., Hayden, V., Menza, R. L., Convery, M., Poon, A., Landeck, M., Zaroff, J. G., Matthay, M. A. 2011; 30 (2): 211-217

    Abstract:

    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 ?-adrenergic receptors (?ARs). Single-nucleotide polymorphisms (SNPs) in ?AR genes have functional effects in vitro and in vivo. We hypothesized that SNPs in ?AR genes would be associated with rates of utilization of donor lung allografts offered for transplantation.Nine hundred fifty-one organ donors were genotyped for 4 amino-acid-coding SNPs in the ?AR genes. Lung allograft utilization was compared among donors stratified by genotypes.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.Genetic variants in the ?AR 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 ?AR agonists may have a role in donor management.

    View details for DOI 10.1016/j.healun.2010.08.011

    View details for Web of Science ID 000286545200015

    View details for PubMedID 20869266

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