Cervera Carlos, Balderramo Domingo, Suárez Belén, Prieto Jhon, Fuster Francisco, Linares Laura, Fuster Josep, Moreno Asunción, Lozano Francisco, Navasa Miquel
Department of Infectious Diseases, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
Liver Transpl. 2009 Oct;15(10):1217-24. doi: 10.1002/lt.21834.
Mannose-binding lectin (MBL) is a C-type lectin produced mainly by the liver that binds to a wide range of pathogens. Polymorphisms at the promoter and exon 1 of the MBL2 gene are responsible for low serum levels of MBL and have been associated with an increased risk of infections. We prospectively analyzed 95 liver transplant recipients. Well-known functionally relevant polymorphisms of the MBL2 gene of the liver donor were examined by gene sequencing. Infectious events were collected prospectively. No differences in the incidence of infections were found according to the donor MBL2 genotypes. Survival was lower in patients receiving a liver graft from a donor with an exon 1 MBL2 variant genotype, and they had higher infection-related mortality (50% versus 14%, P = 0.040). No differences were found according to other polymorphisms involving the promoter and 5'-untranslated region. When we analyzed bacterial infection episodes, we found that patients receiving a liver from a donor with an exon 1 variant genotype had a higher incidence of septic shock (46% versus 11%, P = 0.004). Independent variables associated with graft or patient survival were as follows: receiving a graft from a donor with an exon 1 MBL2 variant genotype [adjusted hazard ratio (aHR), 9.64; 95% confidence interval (CI), 2.59-36.0], the Model for End-Stage Liver Disease score (aHR, 1.14; 95% CI, 1.05-1.23), and bacterial infections (aHR, 11.1; 95% CI, 2.73-44.9). Liver transplantation from a donor with a variant MBL2 exon 1 genotype was associated with a worse prognosis, mainly because of infections of higher severity.
甘露糖结合凝集素（MBL）是一种主要由肝脏产生的C型凝集素，可与多种病原体结合。MBL2基因启动子和外显子1的多态性导致血清MBL水平较低，并与感染风险增加有关。我们对95例肝移植受者进行了前瞻性分析。通过基因测序检测肝供体MBL2基因中众所周知的功能相关多态性。前瞻性收集感染事件。根据供体MBL2基因型，未发现感染发生率有差异。接受具有外显子1 MBL2变异基因型供体肝脏移植的患者生存率较低，且感染相关死亡率较高（50%对14%，P = 0.040）。根据涉及启动子和5'非翻译区的其他多态性未发现差异。当我们分析细菌感染发作时，发现接受具有外显子1变异基因型供体肝脏的患者发生感染性休克的发生率较高（46%对11%，P = 0.004）。与移植物或患者生存相关的独立变量如下：接受具有外显子1 MBL2变异基因型供体的移植物[调整后风险比（aHR），9.64；95%置信区间（CI），2.59 - 36.0]、终末期肝病模型评分（aHR，1.14；95% CI，1.05 - 1.23）和细菌感染（aHR，11.1；95% CI，2.73 - 44.9）。来自具有MBL2外显子1变异基因型供体的肝移植与较差的预后相关，主要是因为感染的严重程度较高。
