title: Gene polymorphisms impact the risk of rejection with hemodynamic compromise: a multicenter study.
abstract: BACKGROUND
  Rejection with hemodynamic compromise (RHC) is associated with high mortality in heart recipients. This study investigates the association between genetic polymorphisms and RHC in pediatric heart recipients.
  
  
  METHODS
  Data from 532 pediatric heart recipients from six centers in the Pediatric Heart Transplant Study were analyzed for time to RHC by recipient race, age at transplantation, and genotype at 13 genetic polymorphisms (TNF-α A-308G, IL-6 G-174C, INF-γ T+874A, IL-10 G-1082A, C-819T, and C-592A; FAS A-670G, FASL C-843T, and ACE I/D; and VEGF A-2578C, C-1451T, C+405G, and -2549 I/D).
  
  
  RESULTS
  RHC occurred in 126 (23.7%) patients during the study period. Adjusting for age and race, IL-10 G-1082A, FAS A-670G, and ACE I/D genotypes were associated with RHC. IL-10 G-1082A GG genotype was associated with decreased risk of RHC with an adjusted hazard ratio (HR) of 0.49 (95% confidence interval [CI], 0.27-0.90; P=0.020). FAS A-670G AA genotype was associated with increased risk of RHC with an adjusted HR of 1.84 (95% CI, 1.25-2.69; P=0.002). ACE II genotype was associated with decreased risk of RHC with an adjusted HR of 0.58 (95% CI, 0.36-0.95; P=0.031).
  
  
  CONCLUSIONS
  Recipients with a high anti-inflammatory and immune-regulatory genetic profile (high interleukin-10) were protected from RHC. Conversely, recipients with a pro-apoptotic genetic profile (high Fas) or high angiotensin-1-converting enzyme producing genotype were at increased risk of RHC. This represents progress toward understanding the genetic risk factors of posttransplantation outcomes in pediatric heart recipients.
authors.affiliation: Department of Pathology, Thomas E. Starzl Transplant Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Diana M
authors.initials: DM
authors.lastname: Girnita
authors.forename: Erin L
authors.initials: EL
authors.lastname: Ohmann
authors.forename: Maria M
authors.initials: MM
authors.lastname: Brooks
authors.forename: Steven A
authors.initials: SA
authors.lastname: Webber
authors.forename: Gilbert J
authors.initials: GJ
authors.lastname: Burckart
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Sarangarajan
authors.initials: S
authors.lastname: Ranganathan
authors.forename: Richard
authors.initials: R
authors.lastname: Chinnock
authors.forename: Charles
authors.initials: C
authors.lastname: Canter
authors.forename: Linda
authors.initials: L
authors.lastname: Addonizio
authors.forename: Daniel
authors.initials: D
authors.lastname: Bernstein
authors.forename: James K
authors.initials: JK
authors.lastname: Kirklin
authors.forename: David C
authors.initials: DC
authors.lastname: Naftel
authors.forename: Adriana
authors.initials: A
authors.lastname: Zeevi
mesh_terms: D000293:Adolescent; D000085962:Angiotensin-Converting Enzyme 2; D017209:Apoptosis; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006084:Graft Rejection / Q000235:genetics*; D016027:Heart Transplantation / Q000009:adverse effects* / Q000379:methods; D006439:Hemodynamics; D006801:Humans; D007107:Immune System; D007223:Infant; D016753:Interleukin-10 / Q000378:metabolism; D008297:Male; D008957:Models, Genetic; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: D016753:Interleukin-10; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2