Prevalence of CCR5 Δ32 polymorphism in long-term survivors of heart transplantation
Prevalence of CCR5 Δ32 polymorphism in long-term survivors of heart transplantation
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DOI：
10.1016/j.trim.2006.11.004
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发表时间：
2007-04-01
影响因子：
1.5
通讯作者：
Hetzer, Roland
中科院分区：
文献类型：
--
作者：
Hummel, Manfred;Bara, Christoph;Hetzer, Roland
背景：CC 趋化因子受体 5 (CCR5) 有助于实体器官移植后的同种免疫反应。在 CCR5 Delta 32 突变纯合个体中，受体失活，排斥过程中淋巴细胞的募集和白细胞运输受到抑制。尽管存在相互矛盾的数据，但在纯合 CCR5 Delta 32 患者中观察到肾移植后移植物存活率显着改善。为了确定 CCR5 Delta 32 纯合心脏移植受者与具有正常功能的 CCR 受体的受者相比是否也可能受益，在心脏移植后长期存活的一大群患者中检查了 CCR5 Delta 32 突变患者的比例。方法：在心脏移植后存活 >= 7 年的患者中确定了 CCR5 基因型的患病率。通过聚合酶链反应（PCR）集中进行基因分型。结果：德国三个心脏移植中心总共招募了 555 名患者。其中，442 名患者 (79.6%) 为野生型等位基因纯合子，106 名患者 (19.1%) 为 CCR5 Delta 32 杂合子，7 名患者 (1.3%) 为 CCR5 Delta 32 纯合子。研究人群中 CCR5 Delta 32 纯合性的发生率与正常人群中估计的发生率之间没有观察到统计学上的显着差异。结论：在没有对照臂的情况下，无法确定 CCR5 Delta 32 等位基因的纯合携带者在心脏移植后是否会获得长期生存获益，而心脏移植受者中 CCR5 Delta 32 等位基因的代表性不足可能会掩盖这种获益。为了回答这个问题，需要确定等待心脏移植的患者中 CCR5 Delta 32 纯合性的患病率。 (C) 2006 Elsevier B.V. 保留所有权利。
Background: CC chemokine receptor 5 (CCR5) contributes to the alloimmune response following solid organ transplantation. In individuals homozygous for the CCR5 Delta 32 mutation, the receptor is inactive and lymphocyte recruitment and leukocyte trafficking during rejection are inhibited. A significant improvement in graft survival following renal transplantation has been observed in homozygous CCR5 Delta 32 patients, although conflicting data exist. To determine whether CCR5 Delta 32 homozygous heart transplant recipients may also benefit compared to those with a normally functioning CCR receptor, the proportion of patients with CCR5 Delta 32 mutation was examined in a large cohort of patients surviving for a long period after heart transplantation.Methods: The prevalence of CCR5 genotype was identified in patients who had survived >= 7 years after heart transplantation. Genotyping was performed centrally by polymerase chain reaction (PCR).Results: A total of 555 patients were recruited at three heart transplant centers in Germany. Of these, 442 patients (79.6%) were homozygous for the wild-type allele, 106 (19.1%) were heterozygous for CCR5 Delta 32 and 7 (1.3%) were homozygous for CCR5 Delta 32. No statistically significantly differences were observed between the incidence of CCR5 Delta 32 homozygosity in the study population and the estimated incidence in the normal population.Conclusions: In the absence of a control arm, it cannot be established if homozygous carriers of the CCR5 Delta 32 allele experience a long-term survival benefit following heart transplantation that may be masked by underrepresentation of the CCR5 Delta 32 allele in recipients of a heart transplant. To answer this question, the prevalence of CCR5 Delta 32 homozygosity needs to be established in patients awaiting heart transplantation. (C) 2006 Elsevier B.V. All rights reserved.