Gene Expression Profiling to Study Racial Differences after Heart Transplantation

BACKGROUND: The basis for increased mortality after heart transplantation in African Americans and other non-Caucasian racial groups is poorly defined. We hypothesized that increased risk of adverse events is driven by biological factors. To test this hypothesis in the IMAGE study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or re-transplantation varied by race as a function of calcineurin inhibitor levels and gene expression profile (GEP) scores. METHODS: We determined 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 similar between races. Of patients receiving tacrolimus, other non-Caucasians had higher GEP scores than the other racial groups. African American recipients demonstrated a unique decrease in expression of the FLT3 gene in response to higher tacrolimus levels. CONCLUSIONS: African Americans and other non-Caucasian heart transplant recipients were 2.5–3 times 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 less effectively inhibited at similar tacrolimus levels in minority racial groups.