Objective: This study aimed to investigate the role and clinical significance of MUC4 gene mutations in thrombotic events in patients with classic paroxysmal nocturnal hemoglobinuria (PNH) patients. Methods: A retrospective analysis was conducted on the clinical data and gene sequencing results of 45 patients with classic PNH admitted to the Department of Hematology, Tianjin Medical University General Hospital, from June 2018 to February 2022. MUC4 gene mutations in patients with classic PNH were summarized, and the risk factors for thrombotic events in these patients were analyzed. Additionally, the effects of MUC4 gene mutations on the cumulative incidence and survival of thrombotic events in patients with classic PNH were determined. Results: The detection rate of MUC4 gene mutations in patients with classic PNH who experienced thrombotic events (thrombotic group) was 68.8% (11/16), which was significantly higher than that in the non-thrombotic group [10.3% (3/29) ] (P<0.001). All mutations occurred in exon 2. MUC4 mutation (OR=20.815, P=0.010) was identified as an independent risk factor for thrombotic events in patients with classic PNH. The cumulative incidence of thrombotic events was 78.6% (11/14) in the MUC4 gene mutation group (mutation group) and 16.1% (5/31) in the non-mutation group, showing a statistically significant difference between the two groups (P<0.001). Survival analysis showed a lower overall survival (OS) rate in the thrombotic group compared with that in the non-thrombotic group [ (34.4±25.2) % vs. (62.7±19.3) % ] (P=0.045). The OS rate of patients was (41.7±29.9) % in the mutation group and (59.1±18.3) % in the non-mutation group (P=0.487) . Conclusion: MUC4 gene mutations are associated with an increased incidence of thrombotic events in classic PNH patients, highlighting their role as independent risk factors for thrombosis in this population. These mutations can be considered a novel predictive factor that aids in evaluating the risk of thrombosis in patients with classic PNH.
目的： 探讨MUC4基因突变在经典型阵发性睡眠性血红蛋白尿症（PNH）患者血栓事件中的作用及临床意义。 方法： 回顾性分析2018年6月至2022年2月天津医科大学总医院血液科收治的45例经典型PNH患者的临床资料和基因测序结果，总结经典型PNH患者MUC4基因突变情况，分析经典型PNH患者血栓事件的危险因素，明确MUC4基因突变对经典型PNH患者血栓事件累积发生率和生存的影响。 结果： 经典型PNH合并、不合并血栓事件患者的MUC4突变检出率分别为68.8%（11/16）、10.3%（3/29）（P<0.001），突变均发生在2号外显子。MUC4突变（OR＝20.815，P＝0.010）是经典型PNH患者血栓事件的独立危险因素，MUC4突变组和无MUC4突变组血栓事件累积发生率分别为78.6%（11/14）和16.1%（5/31），两组比较差异有统计学意义（P<0.001）。生存分析显示合并、不合并血栓事件患者总生存（OS）率分别为（34.4±25.2）%、（62.7±19.3）%（P＝0.045）；合并、不合并MUC4突变患者的OS率分别为（41.7±29.9）%、（59.1±18.3）%（P＝0.487）。 结论： MUC4基因突变的经典型PNH患者血栓事件发生率高，MUC4突变是经典型PNH患者血栓事件的独立危险因素。MUC4基因突变可作为新的评估经典型PNH患者血栓形成风险的预测因素。.
Keywords: Gene, MUC4; Paroxysmal nocturnal hemoglobinuria; Thrombotic events.