TY - JOUR
T1 - Association of genetic polymorphisms and risk of late post-transplantation infection in pediatric heart recipients
AU - Ohmann, Erin L.
AU - Brooks, Maria M.
AU - Webber, Steven A.
AU - Girnita, Diana M.
AU - Ferrell, Robert E.
AU - Burckart, Gilbert J.
AU - Chinnock, Richard
AU - Canter, Charles
AU - Addonizio, Linda
AU - Bernstein, Daniel
AU - Kirklin, James K.
AU - Naftel, David C.
AU - Zeevi, Adriana
N1 - Funding Information:
This work was supported by grant 5P50 HL 074 732-05 from the National Heart Lung and Blood Institute , National Institutes of Health . Erin L. Ohmann is supported by funding from Dean Arthur S. Levine, MD , and the Clinical Scientist Training Program at the University of Pittsburgh School of Medicine , and by the Doris Duke Clinical Research Fellowship program . None of the authors has a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose.
PY - 2010/12
Y1 - 2010/12
N2 - 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.
AB - 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.
KW - bacteria infection
KW - genetic polymorphism
KW - pediatric heart transplant
KW - viral infection
UR - https://www.scopus.com/pages/publications/78649334565
U2 - 10.1016/j.healun.2010.07.013
DO - 10.1016/j.healun.2010.07.013
M3 - Article
C2 - 20869265
AN - SCOPUS:78649334565
SN - 1053-2498
VL - 29
SP - 1342
EP - 1351
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 12
ER -