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启动子多态性(-94ins/delATTG)与肾移植后巨细胞病毒感染易感性相关,这可能对 CMV 预防方案有影响。

The Promoter Polymorphism (-94ins/delATTG) Is Associated with Susceptibility to Cytomegalovirus Infection after Kidney Transplantation and Should Have Implications on CMV Prophylaxis Regimens.

机构信息

Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany.

Department of Surgery, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, In der Schornau 23-25, 44892 Bochum, Germany.

出版信息

Cells. 2021 Feb 12;10(2):380. doi: 10.3390/cells10020380.

Abstract

Infections with cytomegalovirus (CMV) are one of the most frequent opportunistic infections in kidney transplant recipients. Current risk-adapted CMV chemoprophylaxis regimens are based almost solely on the donor and recipient CMV serostatus. Of note, the -94ins/delATTG promoter polymorphism was recently associated with a higher risk of CMV infection. Since single genetic association studies suffer from poor reliability for drawing therapeutic implications, we performed this confirmatory study and included 256 kidney transplant recipients from 2007 to 2014 in this retrospective study. Patients were genotyped for the -94ins/delATTG promoter polymorphism and followed up for 12 months. The incidence of CMV infection within 12 months after kidney transplantation was 37.5% (33/88) for the ins/ins, 21.5% (28/130) for the ins/del, and 23.7% (9/38) for the del/del genotypes ( = 0.023). Moreover, we evaluated the time of CMV infection onset. Ins/ins carriers had primarily late-onset CMV infection (median 194 days; interquartile range (IQR) 117-267 days) compared with heterozygous (ins/del; median 158 days; IQR 82-195 days) and homozygous deletion allele carriers (del/del; median 95 days; 84-123 days). Multivariate-restricted Cox regression model confirmed the ins/ins genotype to be an independent risk factor for the development of late-onset CMV infections. These findings should have an impact on post-kidney transplantation CMV chemoprophylaxis regimens.

摘要

巨细胞病毒 (CMV) 感染是肾移植受者中最常见的机会性感染之一。目前基于风险的 CMV 化学预防方案几乎完全基于供体和受体的 CMV 血清状态。值得注意的是,-94ins/delATTG 启动子多态性最近与 CMV 感染风险增加相关。由于单基因关联研究在得出治疗意义方面可靠性较差,因此我们进行了这项验证性研究,并将 2007 年至 2014 年间的 256 名肾移植受者纳入了这项回顾性研究。对患者进行了-94ins/delATTG 启动子多态性基因分型,并进行了 12 个月的随访。肾移植后 12 个月内 CMV 感染的发生率为 ins/ins 基因型 37.5%(33/88),ins/del 基因型 21.5%(28/130),del/del 基因型 23.7%(9/38)(=0.023)。此外,我们还评估了 CMV 感染的发病时间。Ins/ins 携带者主要发生迟发性 CMV 感染(中位数 194 天;四分位距 (IQR) 117-267 天),与杂合子(ins/del;中位数 158 天;IQR 82-195 天)和纯合缺失等位基因携带者(del/del;中位数 95 天;84-123 天)相比。多变量受限 Cox 回归模型证实 ins/ins 基因型是迟发性 CMV 感染发生的独立危险因素。这些发现应该对肾移植后 CMV 化学预防方案产生影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5805/7918124/3e95cea2d0cb/cells-10-00380-g001.jpg

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