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心脏移植长期存活者中CCR5Delta32多态性的患病率

Prevalence of CCR5Delta32 polymorphism in long-term survivors of heart transplantation.

作者信息

Hummel Manfred, Bara Christoph, Hirt Stephan, Haverich Axel, Hetzer Roland

机构信息

German Heart Institute Berlin, Division of Cardiovascular Surgery, Augustenburger Platz 1, 13353 Berlin, Germany.

出版信息

Transpl Immunol. 2007 Apr;17(3):223-6. doi: 10.1016/j.trim.2006.11.004. Epub 2006 Dec 8.

Abstract

BACKGROUND

CC chemokine receptor 5 (CCR5) contributes to the alloimmune response following solid organ transplantation. In individuals homozygous for the CCR5Delta32 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 CCR5Delta32 patients, although conflicting data exist. To determine whether CCR5Delta32 homozygous heart transplant recipients may also benefit compared to those with a normally functioning CCR receptor, the proportion of patients with CCR5Delta32 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 >or=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 CCR5Delta32 and 7 (1.3%) were homozygous for CCR5Delta32. No statistically significantly differences were observed between the incidence of CCR5Delta32 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 CCR5Delta32 allele experience a long-term survival benefit following heart transplantation that may be masked by underrepresentation of the CCR5Delta32 allele in recipients of a heart transplant. To answer this question, the prevalence of CCR5Delta32 homozygosity needs to be established in patients awaiting heart transplantation.

摘要

背景

C-C趋化因子受体5(CCR5)在实体器官移植后的同种免疫反应中起作用。在CCR5Δ32突变纯合子个体中,该受体无活性,排斥反应期间淋巴细胞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CCR5Δ32纯合子患者肾移植后观察到移植物存活率有显著提高。为了确定CCR5Δ32纯合子心脏移植受者与CCR受体功能正常的受者相比是否也能获益,在一大群心脏移植后长期存活的患者中检查了CCR5Δ32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(19.1%)为CCR5Δ32杂合子,7名(1.3%)为CCR5Δ32纯合子。研究人群中CCR5Δ32纯合子的发生率与正常人群的估计发生率之间未观察到统计学上的显著差异。

结论

在没有对照组的情况下,无法确定CCR5Δ32等位基因纯合子携带者在心脏移植后是否经历长期生存获益,这可能因心脏移植受者中CCR5Δ32等位基因的代表性不足而被掩盖。为了回答这个问题,需要确定等待心脏移植患者中CCR5Δ32纯合子的患病率。

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