Girnita Diana M, Brooks Maria M, Webber Steven A, Burckart Gilbert J, Ferrell Robert, Zdanowicz Gina, DeCroo Susan, Smith Louise, Chinnock Richard, Canter Charles, Addonizio Linda, Bernstein Daniel, Kirklin James K, Ranganathan Sarangarajan, Naftel David, Girnita Alin L, Zeevi Adriana
Department of Pathology, Thomas E Starzl Transplant Institute, University of Pittsburgh, PA, USA.
Transplantation. 2008 Jun 15;85(11):1632-9. doi: 10.1097/TP.0b013e3181722edc.
The objective of this study was to determine the association between the genetic polymorphisms of proinflammatory and regulatory cytokines and long-term rates of repeat and late acute rejection episodes in pediatric heart transplant (PHTx) recipients.
Three hundred twenty-three PHTx recipients: 205 White non-Hispanic, 43 Black non-Hispanic, and 75 Hispanic were analyzed for time to first repeat and late acute rejection episodes by race, age at transplantation, and gene polymorphism (interleukin [IL]-6, -174 G/C, IL-10, -1082 G/A, -819 C/T, 592 C/A; vascular endothelial growth factor (VEGF) -2578 C/A, -460 C/T, +405 C/G; tumor necrosis factor alpha (TNF-alpha)-308 G/A).
Recipient black race and older age at transplant were risk factors for both repeat and late rejections, though black race was more significantly related to late rejection (P=0.006). Individually, TNF-alpha high, IL-6 high, VEGF high, and IL-10 low phenotypes did not impact the risk of repeat or late rejection. However, the combination VEGF high/IL-6 high and IL-10 low was associated with increased estimated risk of late rejection (P=0.0004) and only marginally with repeat rejection (P=0.051). In a multivariate analysis, adjusting for age and race, VEGF high/IL-6 high and IL-10 low still remained an independent risk factor for late acute rejection (RR=1.91, P<0.001).
This is the largest multicenter study to document the impact of genetic polymorphism combinations on PHTx recipients' outcome. The high proinflammatory (VEGF high/IL-6 high) and lower regulatory (IL-10 low) cytokine gene polymorphism profile exhibited increased risk for late rejection, irrespective of age and race/ethnicity.
本研究的目的是确定促炎细胞因子和调节性细胞因子的基因多态性与小儿心脏移植（PHTx）受者重复和晚期急性排斥反应的长期发生率之间的关联。
对233名PHTx受者进行分析，其中包括205名非西班牙裔白人、43名非西班牙裔黑人以及75名西班牙裔，分析其首次重复和晚期急性排斥反应发作的时间，分析因素包括种族、移植时年龄以及基因多态性（白细胞介素[IL]-6，-174 G/C；IL-10，-1082 G/A，-819 C/T，592 C/A；血管内皮生长因子（VEGF）-2578 C/A，-460 C/T，+405 C/G；肿瘤坏死因子α（TNF-α）-308 G/A）。
受者的黑人种族以及移植时年龄较大是重复和晚期排斥反应的危险因素，尽管黑人种族与晚期排斥反应的相关性更强（P=0.006）。单独来看，TNF-α高、IL-6高、VEGF高以及IL-10低表型并未影响重复或晚期排斥反应的风险。然而，VEGF高/IL-6高和IL-10低的组合与晚期排斥反应的估计风险增加相关（P=0.0004），与重复排斥反应仅呈边缘相关（P=0.051）。在多变量分析中，校正年龄和种族后，VEGF高/IL-6高和IL-10低仍然是晚期急性排斥反应的独立危险因素（RR=1.91，P<0.001）。
这是记录基因多态性组合对PHTx受者结局影响的最大规模多中心研究。促炎（VEGF高/IL-6高）和调节性（IL-10低）细胞因子基因多态性水平较高的情况显示出晚期排斥反应风险增加，与年龄和种族/民族无关。
