Gene Polymorphisms Impact the Risk of Rejection With Hemodynamic Compromise: A Multicenter Study
Gene Polymorphisms Impact the Risk of Rejection With Hemodynamic Compromise: A Multicenter Study
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DOI：
10.1097/tp.0b013e31821c1e10
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发表时间：
2011-06-27
期刊：
影响因子：
6.2
通讯作者：
Zeevi, Adriana
中科院分区：
文献类型：
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作者：
Girnita, Diana M.;Ohmann, Erin L.;Zeevi, Adriana
背景排斥反应伴血流动力学损害（RHC）与心脏受者的高死亡率相关。本研究旨在探讨遗传多态性与小儿心脏病RHC之间的关系。来自儿科心脏移植研究的6个中心的532名儿科心脏受者的数据通过受者种族、移植时年龄和13种遗传多态性的基因型分析了RHC的时间（TNF-α A-308G、IL-6 G-174C、INF-γ T+874A、IL-10 G-1082A、C-819 T和C-592A; FAS A-670G、FASL C-843 T和ACE I/D;和VEGF A-2578C、C-1451T、C+405G和-2549 I/D）。在研究期间，126例（23.7%）患者发生了RHC。调整年龄和种族后，IL-10 G-1082 A、FAS A-670 G和ACE I/D基因型与RHC相关。IL-10 G-1082 A GG基因型与RHC风险降低相关，校正后的风险比（HR）为0.49（95%置信区间[CI]，0.27-0.90; P=0.020）。FAS A-670 G AA基因型与RHC风险增加相关，校正HR为1.84（95% CI，1.25-2.69; P=0.002）。ACE II基因型与RHC风险降低相关，调整后HR为0.58（95%CI，0.36-0.95; P=0.031）。结论。具有高抗炎和免疫调节基因谱（高白细胞介素-10）的受体受到保护，免受RHC的影响。相反，具有促凋亡基因型（高Fas）或高血管紧张素-1转换酶产生基因型的受体发生RHC的风险增加。这代表了对儿童心脏受者移植后结果遗传危险因素的理解的进步。
Background. Rejection with hemodynamic compromise (RHC) is associated with high mortality in heart recipients. This study investigates the association between genetic polymorphisms and RHC in pediatric heart recipients.Methods. Data from 532 pediatric heart recipients from six centers in the Pediatric Heart Transplant Study were analyzed for time to RHC by recipient race, age at transplantation, and genotype at 13 genetic polymorphisms (TNF-alpha A-308G, IL-6 G-174C, INF-gamma T+874A, IL-10 G-1082A, C-819T, and C-592A; FAS A-670G, FASL C-843T, and ACE I/D; and VEGF A-2578C, C-1451T, C+405G, and -2549 I/D).Results. RHC occurred in 126 (23.7%) patients during the study period. Adjusting for age and race, IL-10 G-1082A, FAS A-670G, and ACE I/D genotypes were associated with RHC. IL-10 G-1082A GG genotype was associated with decreased risk of RHC with an adjusted hazard ratio (HR) of 0.49 (95% confidence interval [CI], 0.27-0.90; P=0.020). FAS A-670G AA genotype was associated with increased risk of RHC with an adjusted HR of 1.84 (95% CI, 1.25-2.69; P=0.002). ACE II genotype was associated with decreased risk of RHC with an adjusted HR of 0.58 (95% CI, 0.36-0.95; P=0.031).Conclusions. Recipients with a high anti-inflammatory and immune-regulatory genetic profile (high interleukin-10) were protected from RHC. Conversely, recipients with a pro-apoptotic genetic profile (high Fas) or high angiotensin-1-converting enzyme producing genotype were at increased risk of RHC. This represents progress toward understanding the genetic risk factors of posttransplantation outcomes in pediatric heart recipients.