Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective study.
Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective study.
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DOI：
10.1186/s12959-023-00548-6
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发表时间：
2023-10-03
影响因子：
3.1
通讯作者：
中科院分区：
文献类型：
--
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蛋白C（PC）基因R189 W和K193 del是中国人群静脉血栓栓塞症（VTE）的热点突变，但近三分之二的患者同时存在其他遗传性或先天性血栓前危险因素。本研究的目的是阐明R189 W或K193 del对VTE风险的独立贡献。490例有VTE个人病史的无关患者和410例健康受试者入组本研究。收集患者的人口学资料、家族史、遗传和获得性血栓形成危险因素等资料并进行统计学分析。PC R189 W和K193 del分别在3/410（0.7%）和7/410（1.7%）健康对照以及27/490（5.5%）和43/490（8.8%）VTE患者中被发现。值得注意的是，约70%的突变携带者与其他遗传或获得性血栓形成因子相结合。在调整了年龄、性别、其他遗传和获得性风险因素后，我们证明R189 W和K193 del分别与VTE风险增加5.781倍和4.365倍相关，这显著低于罕见突变引起的抗凝剂缺乏的血栓前风险。独立的R189 W或K193 del突变与VTE的早发年龄及复发率无关。然而，其他遗传或获得性血栓形成因素的组合对这些后果具有超累加效应。患者的其他危险因素越多，首次发病年龄越小，复发风险越高。R189 W和K193 del突变是中国人群中最常见的PC缺乏症突变，与PROC基因中的其他罕见突变相比，这两种突变对VTE发生的独立贡献有限，但可能与其他遗传缺陷或获得性血栓形成危险因素协同作用，产生最终的严重表型。在线版本包含补充材料，可通过10.1186/s12959-023-00548-6获得。
R189W and K193del of protein C (PC) were hotspot mutations in Chinese population with venous thromboembolism (VTE), but almost two-thirds of patients with above mutations coexisting with other genetically or aquiredly prothrombotic risk factors. The aim of this study is to clarify the independent contributions of R189W or K193del to VTE risk. 490 unrelated patients with a personal history of VTE and 410 healthy participants were enrolled in this study. Data of their demographics, family history, genetic and acquired thrombosis risk factors were collected and statistically analyzed. PC R189W and K193del were identified in 3/410 (0.7%) and 7/410 (1.7%) healthy controls, and in 27/490 (5.5%) and 43/490 (8.8%) patients with VTE, respectively. Notably, about 70% of these mutant carriers combined with other genetic or acquired thrombophilic factors. After adjustment for age, gender, other inherited and acquired risk factors, we demonstrated that R189W and K193del were associated with 5.781-fold and 4.365-fold increased risk of VTE, respectively, which were significantly lower than the prothrombotic risk of anticoagulant deficiencies induced from rare mutations. Independent R189W or K193del mutation was not associated with earlier first-onset age as well as higher recurrent rate of VTE. However, combination of other genetic or acquired thrombophilic factors had supra-additive effects on those consequences. The more additional risk factors the patients had, the younger first-onset ages and higher risk of recurrence would be. As the most frequent mutations for PC deficiency in Chinese population, both R189W and K193del mutations had limited independent contributions to VTE development compared with other rare mutations in PROC gene, but may act in concert with other genetic defects or acquired thrombotic risk factors to produce the final severe phenotype. The online version contains supplementary material available at 10.1186/s12959-023-00548-6.
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DOI：
10.1073/pnas.90.3.1004
发表时间：
1993-02-01
影响因子：
11.1
作者：
DAHLBACK, B;CARLSSON, M;SVENSSON, PJ
通讯作者：
SVENSSON, PJ
影响因子：
2.9
作者：
MESTERS, RM;HEEB, MJ;GRIFFIN, JH
通讯作者：
GRIFFIN, JH
影响因子：
7.5
作者：
Miyata, T;Sakata, T;Kato, H
通讯作者：
Kato, H
影响因子：
6.7
作者：
Ding, Qiulan;Yang, Likui;Rezaie, Alireza R.
通讯作者：
Rezaie, Alireza R.
影响因子：
1.1
作者：
Noguchi, Kenta;Nakazono, Eri;Tsuda, Hiroko
通讯作者：
Tsuda, Hiroko