Differential Gene Expression by Race and Impact on Risk after Heart Transplantation

Purpose African Americans (AA) have worse survival compared to Caucasians post heart transplantation (HTx). The aim of this analysis was to evaluate racial differences in gene expression and the impact on survival and a composite outcome of death, re-Tx, hemodynamic rejection and graft dysfunction in the Outcomes AlloMap Registry (OAR). Methods AA and Caucasians who had a baseline (BL) and at least 1 follow-up (FU) test within the first year of HTx were included. The KM method with delayed entry was used to describe difference in outcomes. Multivariable cox hazard regression was used to evaluate the associations of GEP score, MARCH8, FLT3 and tacrolimus levels with each outcome, and stratified cox models were developed to quantify the race-specific associations. Results Among 992 eligible recipients, 777 (78%) were Caucasian and 215 (22%) AA. Compared to Caucasians, AA were significantly younger (55 vs 59 yrs), with higher rates of DCMP (68% vs 49%), multiorgan Tx (7% vs 1%), sensitization (>10% PRA 17% vs 10%) and HLA mismatches (6 vs. 7, p=0.02). AA had increased adjusted mortality risk HR 1.16, p<0.05 (Fig 1A). Trends for GEP, MARCH8, FLT3 and tacrolimus by race are shown in Fig 1B. In Caucasians, higher tacrolimus was associated with increased mortality HR 1.12, p=0.06; while protective in AA HR 0.58, p<0.005. Caucasians with higher MARCH8 had increased mortality and composite events, BL: HR 2.4, p< 0.001; change in FU from BL: HR 2.2, p< 0.001. In contrast in AA, BL MARCH8 was associated with a decreased risk of composite event HR 0.05, p<0.01. Caucasians with higher BL FLT3 were at a lower risk of mortality HR 0.97, p= 0.053 and composite event HR 0.60, p<0.05. While higher FU FLT3 was associated with a higher mortality risk HR 2.1, p<0.05 and composite event HR 2.5, p<0.01 in AA. Conclusion AA have a significantly higher mortality risk after HTx than Caucasians, even in the low risk OAR population. AA and Caucasians had differential gene expression of MARCH8 and FLT3 genes and differential risk associated with the expression of these genes. African Americans (AA) have worse survival compared to Caucasians post heart transplantation (HTx). The aim of this analysis was to evaluate racial differences in gene expression and the impact on survival and a composite outcome of death, re-Tx, hemodynamic rejection and graft dysfunction in the Outcomes AlloMap Registry (OAR). AA and Caucasians who had a baseline (BL) and at least 1 follow-up (FU) test within the first year of HTx were included. The KM method with delayed entry was used to describe difference in outcomes. Multivariable cox hazard regression was used to evaluate the associations of GEP score, MARCH8, FLT3 and tacrolimus levels with each outcome, and stratified cox models were developed to quantify the race-specific associations. Among 992 eligible recipients, 777 (78%) were Caucasian and 215 (22%) AA. Compared to Caucasians, AA were significantly younger (55 vs 59 yrs), with higher rates of DCMP (68% vs 49%), multiorgan Tx (7% vs 1%), sensitization (>10% PRA 17% vs 10%) and HLA mismatches (6 vs. 7, p=0.02). AA had increased adjusted mortality risk HR 1.16, p<0.05 (Fig 1A). Trends for GEP, MARCH8, FLT3 and tacrolimus by race are shown in Fig 1B. In Caucasians, higher tacrolimus was associated with increased mortality HR 1.12, p=0.06; while protective in AA HR 0.58, p<0.005. Caucasians with higher MARCH8 had increased mortality and composite events, BL: HR 2.4, p< 0.001; change in FU from BL: HR 2.2, p< 0.001. In contrast in AA, BL MARCH8 was associated with a decreased risk of composite event HR 0.05, p<0.01. Caucasians with higher BL FLT3 were at a lower risk of mortality HR 0.97, p= 0.053 and composite event HR 0.60, p<0.05. While higher FU FLT3 was associated with a higher mortality risk HR 2.1, p<0.05 and composite event HR 2.5, p<0.01 in AA. AA have a significantly higher mortality risk after HTx than Caucasians, even in the low risk OAR population. AA and Caucasians had differential gene expression of MARCH8 and FLT3 genes and differential risk associated with the expression of these genes.