Khush Kiran K, Pham Michael X, Teuteberg Jeffrey J, Kfoury Abdallah G, Deng Mario C, Kao Andrew, Anderson Allen S, Cotts William G, Ewald Gregory A, Baran David A, Hiller David, Yee James, Valantine Hannah A
Stanford University School of Medicine, Stanford, California.
Stanford University School of Medicine, Stanford, California.
J Heart Lung Transplant. 2015 Jul;34(7):970-7. doi: 10.1016/j.healun.2015.01.987. Epub 2015 Feb 7.
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 biologic factors. To test this hypothesis in the Invasive Monitoring Attenuation through Gene Expression (IMAGE) study, we determined whether the event rate of the primary outcome of acute rejection, graft dysfunction, death, or retransplantation varied by race as a function of calcineurin inhibitor (CNI) levels and gene expression profile (GEP) scores.
We determined the event rate of the primary outcome, comparing racial groups, stratified by time after 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.
In 580 patients monitored for a median of 19 months, the incidence of the primary end point was 18.3% in African Americans, 22.2% in other non-Caucasians, and 8.5% in Caucasians (p < 0.001). There were small but significant correlations of race and tacrolimus trough levels to the GEP score. Tacrolimus levels were similar among the 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.
African Americans and other non-Caucasian heart transplant recipients were 2.5-times to 3-times more likely than Caucasians to experience outcome events in the Invasive Monitoring Attenuation through Gene Expression study. 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.
非裔美国人及其他非白种人种族群体心脏移植后死亡率增加的原因尚不明确。我们推测不良事件风险增加是由生物学因素驱动的。为了在通过基因表达进行侵入性监测衰减（IMAGE）研究中验证这一假设，我们确定了急性排斥、移植物功能障碍、死亡或再次移植等主要结局的事件发生率是否因种族而异，这一差异是作为钙调神经磷酸酶抑制剂（CNI）水平和基因表达谱（GEP）评分的函数。
我们确定主要结局的事件发生率，比较不同种族群体，并按移植后的时间进行分层。使用逻辑回归计算不同种族群体之间的相对风险，使用线性模型测量CNI水平和GEP评分对种族的依赖性。
在中位随访19个月的580例患者中，主要终点的发生率在非裔美国人中为18.3%，在其他非白种人中为22.2%，在白种人中为8.5%（p<0.001）。种族和他克莫司谷浓度与GEP评分之间存在虽小但显著的相关性。不同种族之间他克莫司水平相似。在接受他克莫司治疗的患者中，其他非白种人的GEP评分高于其他种族群体。非裔美国受者在较高他克莫司水平下表现出FLT3基因表达的独特下降。
在通过基因表达进行侵入性监测衰减研究中，非裔美国人和其他非白种人心脏移植受者发生结局事件的可能性是白种人的2.5倍至3倍。不良结局风险增加可能部分归因于同种免疫反应的生物学特性，在少数种族群体中，相似的他克莫司水平对其抑制效果较差。
