Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective study
Abstract Background 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 clarif...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | Thrombosis Journal |
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| Online Access: | https://doi.org/10.1186/s12959-023-00548-6 |
| _version_ | 1797451790040432640 |
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| author | Lei Li Jian Li Xi Wu Wenman Wu Qiulan Ding Baohua Qian Xuefeng Wang |
| author_facet | Lei Li Jian Li Xi Wu Wenman Wu Qiulan Ding Baohua Qian Xuefeng Wang |
| author_sort | Lei Li |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results 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. Conclusions 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. |
| first_indexed | 2024-03-09T14:59:29Z |
| format | Article |
| id | doaj.art-d6b41ce42d444e9091c4ed7b064d672e |
| institution | Directory Open Access Journal |
| issn | 1477-9560 |
| language | English |
| last_indexed | 2024-03-09T14:59:29Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Thrombosis Journal |
| spelling | doaj.art-d6b41ce42d444e9091c4ed7b064d672e2023-11-26T14:00:31ZengBMCThrombosis Journal1477-95602023-10-0121111010.1186/s12959-023-00548-6Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective studyLei Li0Jian Li1Xi Wu2Wenman Wu3Qiulan Ding4Baohua Qian5Xuefeng Wang6Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineClinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Transfusion Medicine, Changhai Hospital, Second Military Medical UniversityDepartment of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineAbstract Background 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. Methods 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. Results 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. Conclusions 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.https://doi.org/10.1186/s12959-023-00548-6Protein C deficiencyHotspot mutationVenous thromboembolismRisk factors |
| spellingShingle | Lei Li Jian Li Xi Wu Wenman Wu Qiulan Ding Baohua Qian Xuefeng Wang Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective study Thrombosis Journal Protein C deficiency Hotspot mutation Venous thromboembolism Risk factors |
| title | Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective study |
| title_full | Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective study |
| title_fullStr | Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective study |
| title_full_unstemmed | Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective study |
| title_short | Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective study |
| title_sort | evaluation of prothrombotic risk of two proc hotspot mutations arg189trp and lys193del in chinese population a retrospective study |
| topic | Protein C deficiency Hotspot mutation Venous thromboembolism Risk factors |
| url | https://doi.org/10.1186/s12959-023-00548-6 |
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