MUC4基因突变在经典型阵发性睡眠性血红蛋白尿症患者血栓事件中的作用及临床意义

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.