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

[摘要] 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 occuring >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 pnmer-polymerase chain reaction and/or sequencing Significant associations in univariable analyses were tested m multivariable Cox regression models RESULTS Late infection was common, with 48 7% of patients expenencing >= 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 bactenal and viral (hazard ratio [HR] 0 89-092 per 1 year age increase, p < 0 001) Adjusting for age, race and transplant etiology, late bactenal infection was associated with HMOX1 A + 326G AG and GG genotypes (HR 241 95% confidence interval [CI] 1 35-430 p = 0 003) and GZMB A-295G AA genotype (HR 1 47, 95% CI, 1 03-2 1, p = 0 036) Late viral mfection was associated with FAS A-670G GG genotype (FIR 1 42,95% CI, 1 00-2 00, p = 0 050) in the adjusted model and with CTL44 A+49G AA and AG genotypes (HR, 1 49 95% CI 1 02-2 19 p = 0 041) m umvariable 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 CTL44 a regulator of T-cell activation This represents progress toward understanding the clinical and genetic risk factors of outcomes after transplantation J Heart Lung Transplant 2010 29 1342-51 (C) 2010 International Society for Heart and Lung Transplantation All rights reserved

[发布日期] 2010-12-01

[关键词] pediatric heart transplant;bacteria infection;viral infection;genetic polymorphism