Association of genetic polymorphisms and risk of late post-transplantation infection in pediatric heart recipients

J Heart Lung Transplant. 2010 Dec;29(12):1342-51. doi: 10.1016/j.healun.2010.07.013.


Background: Late infections are common causes of morbidity and mortality after pediatric heart transplantation. In this multicenter study from 6 centers, we investigated the association between genetic polymorphisms (GPs) in immune response genes and late post-transplantation infections in 524 patients.

Methods: Late infection was defined as a clinical infectious process occurring >60 days after transplantation and requiring hospitalization, intravenous antimicrobial therapy, or a life-threatening infection requiring oral therapy. All patients provided a blood sample for GP analyses of 18 GPs in cytokine, growth factor, and effector molecule genes by single specific primer-polymerase chain reaction and/or sequencing. Significant associations in univariable analyses were tested in multivariable Cox regression models.

Results: Late infection was common, with 48.7% of patients experiencing ≥ 1 late infection, 25.2% had ≥ 1 late bacterial infection, and 30.5% had ≥ 1 late viral infection. Older age at transplantation was a protective factor for late infection, both bacterial and viral (hazard ratio [HR] 0.89-0.92 per 1-year age increase, p < 0.001). Adjusting for age, race, and transplant etiology, late bacterial infection was associated with HMOX1 A+326G AG and GG genotypes (HR, 2.41, 95% confidence interval [CI] 1.35-4.30; p = 0.003) and GZMB A-295G AA genotype (HR, 1.47; 95% CI; 1.03-2.1; p = 0.036). Late viral infection was associated with FAS A-670G GG genotype (HR, 1.42; 95% CI, 1.00-2.00; p = 0.050) in the adjusted model and with CTLA4 A+49G AA and AG genotypes (HR, 1.49; 95% CI, 1.02-2.19; p = 0.041) in univariable analysis.

Conclusion: We found an association between late bacterial infection and GP of HMOX1, which may control macrophage activation. A weaker association was also found between late viral infection and GP of CTLA4, a regulator of T-cell activation. This represents progress toward understanding the clinical and genetic risk factors of outcomes after transplantation.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antigens, CD / genetics
  • Bacterial Infections / genetics*
  • CTLA-4 Antigen
  • Child
  • Child, Preschool
  • Cohort Studies
  • Female
  • Genes, MHC Class II / genetics*
  • Genetic Predisposition to Disease*
  • Genotype
  • Heart Transplantation / immunology*
  • Heme Oxygenase-1 / genetics
  • Humans
  • Infant
  • Male
  • Polymorphism, Genetic / immunology*
  • Risk Factors
  • Virus Diseases / genetics*


  • Antigens, CD
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • HMOX1 protein, human
  • Heme Oxygenase-1