Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population
Plasma levels of the anticoagulant cofactor protein S and PROS1 mutation are reported to impart increased risk of thromboembolism in European and south east Asian populations, but the relationship is not yet documented in Han Chinese in population-based study. Therefore, we undertook a case-control...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.796755/full |
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| author | Yingying Wu Jingdi Liu Jingdi Liu Wei Zeng Bei Hu Bei Hu Yu Hu Yu Hu Liang V. Tang Liang V. Tang |
| author_facet | Yingying Wu Jingdi Liu Jingdi Liu Wei Zeng Bei Hu Bei Hu Yu Hu Yu Hu Liang V. Tang Liang V. Tang |
| author_sort | Yingying Wu |
| collection | DOAJ |
| description | Plasma levels of the anticoagulant cofactor protein S and PROS1 mutation are reported to impart increased risk of thromboembolism in European and south east Asian populations, but the relationship is not yet documented in Han Chinese in population-based study. Therefore, we undertook a case-control study of this relationship among patients with venous thromboembolism, and probed the genetic factors contributing to low protein S deficiency. Among the 603 consecutively recruited venous thromboembolism patients, 51 (8.5%) proved to be deficient in free protein S antigen (lower than 38.6 U/dl), among whom 30 cases were identified to have a causative mutation by direct sequencing. In contrast, six cases (1.0%) of the 584 healthy controls had low free antigen levels, among whom direct sequencing confirmed disease-causing gene mutations in four controls (0.7%). After adjusting for age and gender, the odds ratio of developing venous thromboembolism in individuals with protein S deficiency based on free protein S tests was 8.1 (95% CI = 3.6–19.9, P < 0.001). Gene sequencing yielded 24 different heterozygous mutations in the 34 participants, of which 13 were newly described. 17 (50%) of the 34 mutations in our study cohort occurred in exons 12 and 13, indicating the LGR2 domain to be a hotspot mutation region for the protein. These findings are conducive to the clinical application of protein S assays for the molecular diagnosis of thrombophilia. |
| first_indexed | 2024-12-12T08:41:24Z |
| format | Article |
| id | doaj.art-3331c6cc8fa54140ad874c90e0d91107 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-12T08:41:24Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-3331c6cc8fa54140ad874c90e0d911072022-12-22T00:30:46ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2022-06-01810.3389/fcvm.2021.796755796755Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese PopulationYingying Wu0Jingdi Liu1Jingdi Liu2Wei Zeng3Bei Hu4Bei Hu5Yu Hu6Yu Hu7Liang V. Tang8Liang V. Tang9Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Clinical and Research Centre of Thrombosis and Haemostasis, Wuhan, ChinaDepartment of Radiation and Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Clinical and Research Centre of Thrombosis and Haemostasis, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Clinical and Research Centre of Thrombosis and Haemostasis, Wuhan, ChinaInstitute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaHubei Clinical and Research Centre of Thrombosis and Haemostasis, Wuhan, ChinaPlasma levels of the anticoagulant cofactor protein S and PROS1 mutation are reported to impart increased risk of thromboembolism in European and south east Asian populations, but the relationship is not yet documented in Han Chinese in population-based study. Therefore, we undertook a case-control study of this relationship among patients with venous thromboembolism, and probed the genetic factors contributing to low protein S deficiency. Among the 603 consecutively recruited venous thromboembolism patients, 51 (8.5%) proved to be deficient in free protein S antigen (lower than 38.6 U/dl), among whom 30 cases were identified to have a causative mutation by direct sequencing. In contrast, six cases (1.0%) of the 584 healthy controls had low free antigen levels, among whom direct sequencing confirmed disease-causing gene mutations in four controls (0.7%). After adjusting for age and gender, the odds ratio of developing venous thromboembolism in individuals with protein S deficiency based on free protein S tests was 8.1 (95% CI = 3.6–19.9, P < 0.001). Gene sequencing yielded 24 different heterozygous mutations in the 34 participants, of which 13 were newly described. 17 (50%) of the 34 mutations in our study cohort occurred in exons 12 and 13, indicating the LGR2 domain to be a hotspot mutation region for the protein. These findings are conducive to the clinical application of protein S assays for the molecular diagnosis of thrombophilia.https://www.frontiersin.org/articles/10.3389/fcvm.2021.796755/fullprotein S deficiencyvenous thromboembolismgene mutationodds ratioChinese population |
| spellingShingle | Yingying Wu Jingdi Liu Jingdi Liu Wei Zeng Bei Hu Bei Hu Yu Hu Yu Hu Liang V. Tang Liang V. Tang Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population Frontiers in Cardiovascular Medicine protein S deficiency venous thromboembolism gene mutation odds ratio Chinese population |
| title | Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population |
| title_full | Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population |
| title_fullStr | Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population |
| title_full_unstemmed | Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population |
| title_short | Protein S Deficiency and the Risk of Venous Thromboembolism in the Han Chinese Population |
| title_sort | protein s deficiency and the risk of venous thromboembolism in the han chinese population |
| topic | protein S deficiency venous thromboembolism gene mutation odds ratio Chinese population |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.796755/full |
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