Background The basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. the event rate of the primary outcome comparing racial groups stratified by time post-transplant. Logistic regression was used to compute the relative risk across racial groups and linear modeling was used to measure the dependence of CNI levels and GEP score on race. Results In 580 patients followed for a median of 19 months the incidence of the primary endpoint in African Americans other non-Caucasians and Caucasians was 18.3% 22.2% and 8.5% respectively (p<0.001). There were small but significant correlations of race and tacrolimus trough levels to GEP score. Tacrolimus levels were comparable between races. Of patients receiving tacrolimus other Geniposide non-Caucasians had higher GEP scores than the other racial groups. African American recipients demonstrated a unique decrease in expression Geniposide of the FLT3 gene in response to higher tacrolimus levels. Conclusions African Americans and other non-Caucasian heart transplant recipients were 2.5-3 occasions more likely than Caucasians to experience outcome events in IMAGE. The increased risk of adverse outcomes may be partly due to the biology of the alloimmune response which is usually less effectively inhibited at comparable tacrolimus levels in minority racial groups. Keywords: Heart transplantation race acute rejection mortality INTRODUCTION Racial disparities in survival after solid organ transplantation were first recognized by Opelz and Terasaki in 1977 when large differences between African American and Caucasian recipients were identified after kidney transplantation.(1) Since then multiple reports have demonstrated worse survival after heart transplantation in African American recipients compared to other racial groups.(2-7) Many reasons have been suggested to account for racial disparities in post-transplant outcomes. These include socioeconomic and educational factors (2) access to high-quality medical care (4) compliance a higher prevalence of co-morbidities such as hypertension in African American recipients (8) and fundamental immunologic differences.(9 10 The Invasive Monitoring Attenuation through Gene Expression (IMAGE) study (11) which examined the clinical utility of monitoring for acute rejection after heart transplantation using peripheral blood gene-expression profiling provided a unique opportunity to study the biology of racial differences in heart transplant outcomes. We sought to determine whether the incidence of acute rejection graft dysfunction death or re-transplantation varied according to race and to elucidate observed racial disparities in outcomes on the basis of immunosuppressive (calcineurin-inhibitor CNI) drug levels and peripheral blood gene-expression patterns. METHODS Study design patients and procedures The IMAGE study was a randomized trial conducted at Geniposide 13 U.S. heart transplant centers between January 2005 and October 2009. The study design and procedures have been described previously.(11 12 Adult heart transplant recipients between 6 months and 5 years after Geniposide transplant were eligible for enrollment and were randomly assigned to undergo monitoring for rejection by means of gene-expression profiling (GEP) Geniposide or routine endomyocardial biopsies (EMB). Patients assigned to the EMB group also had blood samples taken for GEP testing. This study populace (n = 602) was comprised of 12% African Americans and 6% other non- Caucasian participants TM4SF18 and compliance with medical therapies and rejection surveillance was closely monitored throughout the study period by trial coordinators. Data on medications and laboratory results enabled us to examine differences Geniposide in immunosuppressive drug doses and CNI trough blood levels between racial groups. Finally data on composite gene expression (AlloMap) scores and expression of each of the 11 genes comprising this test were available. These individual genes were originally selected to distinguish immune activation associated with acute rejection from a quiescent state. Analysis of IMAGE study data thereby enabled us to correlate clinical outcomes in different races with individual gene expression which may provide insight into the biology of racial differences in transplant.