title: The 4G/4G genotype of the PAI-1 (serpine-1) 4G/5G polymorphism is associated with decreased lung allograft utilization.
abstract: Widespread thrombi are found among donor lungs rejected for transplantation. The 4G/5G polymorphism in the plasminogen activator inhibitor (PAI-1) gene impacts transcription and the 4G allele is associated with increased PAI-1 levels. We hypothesized that the 4G/4G genotype would be associated with decreased lung graft utilization, potentially because of worse oxygenation in the donor. We genotyped donors managed by the California Transplant Donor Network from 2001 to 2008 for the 4G/5G polymorphism in the PAI-1 gene. Non-Hispanic donors from 2001 to 2005 defined the discovery cohort (n = 519), whereas donors from 2006 to 2008 defined the validation cohort (n = 369). We found, that the odds of successful lung utilization among Non-Hispanic white donors were lower among donors with the 4G/4G genotype compared to those without this genotype in both the discovery (OR = 0.55, 95% CI = 0.3-0.9, p = 0.02) and validation (OR = 0.5, 95% CI = 0.3-0.9, p = 0.03) cohorts. This relationship was independent of age, gender, cause of death, drug use and history of smoking. Donors with the 4G/4G genotype also had a lower PaO2/FiO2 ratio (p = 0.03) and fewer donors with the 4G/4G genotype achieved the threshold PaO2/FiO2 ratio ≥ 300 (p = 0.05). These findings suggest a role for impaired fibrinolysis resulting in worse gas exchange and decreased donor utilization.
authors.affiliation: Department of Pediatrics, University of California, San Francisco, CA, USA. anil.sapru@ucsf.edu
authors.forename: A
authors.initials: A
authors.lastname: Sapru
authors.forename: J G
authors.initials: JG
authors.lastname: Zaroff
authors.forename: L
authors.initials: L
authors.lastname: Pawlikowska
authors.forename: K D
authors.initials: KD
authors.lastname: Liu
authors.forename: K K
authors.initials: KK
authors.lastname: Khush
authors.forename: L A
authors.initials: LA
authors.lastname: Baxter-Lowe
authors.forename: V
authors.initials: V
authors.lastname: Hayden
authors.forename: R L
authors.initials: RL
authors.lastname: Menza
authors.forename: M
authors.initials: M
authors.lastname: Convery
authors.forename: V
authors.initials: V
authors.lastname: Lo
authors.forename: A
authors.initials: A
authors.lastname: Poon
authors.forename: H
authors.initials: H
authors.lastname: Kim
authors.forename: W L
authors.initials: WL
authors.lastname: Young
authors.forename: J
authors.initials: J
authors.lastname: Kukreja
authors.forename: M A
authors.initials: MA
authors.lastname: Matthay
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D017395:Plasminogen Activator Inhibitor 1