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

Erin L. Ohmann, Maria M. Brooks, Steven A. Webber, Diana M. Girnita, Robert E. Ferrell, Gilbert J. Burckart, Richard Chinnock, Charles Canter, Linda Addonizio, Daniel Bernstein, James K. Kirklin, David C. Naftel, Adriana Zeevi

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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] 0.890.92 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] 1.354.30; p = 0.003) and GZMB A-295G AA genotype (HR, 1.47; 95% CI; 1.032.1; p = 0.036). Late viral infection was associated with FAS A-670G GG genotype (HR, 1.42; 95% CI, 1.002.00; p = 0.050) in the adjusted model and with CTLA4 A+49G AA and AG genotypes (HR, 1.49; 95% CI, 1.022.19; 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.

Original languageEnglish
Pages (from-to)1342-1351
Number of pages10
JournalJournal of Heart and Lung Transplantation
Volume29
Issue number12
DOIs
StatePublished - Dec 2010

Keywords

  • bacteria infection
  • genetic polymorphism
  • pediatric heart transplant
  • viral infection

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