Dysfunction of protein C anticoagulant system, main genetic risk factor for venous thromboembolism in Northeast Asians

2013 ◽  
Vol 37 (1) ◽  
pp. 56-65 ◽  
Author(s):  
Tong Yin ◽  
Toshiyuki Miyata
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Genetic Risk ◽  
Protein C ◽  
Genetic Risk Factor ◽  
Anticoagulant System

Protein S K196E mutation, a genetic risk factor for venous thromboembolism, is limited to Japanese

2013 ◽  
Vol 132 (2) ◽  
pp. 314-315 ◽  
Author(s):  
Wanyang Liu ◽  
Tong Yin ◽  
Hiroko Okuda ◽  
Kouji H. Harada ◽  
Yang Li ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Genetic Risk ◽  
Protein S ◽  
Genetic Risk Factor

scholarly journals ELISA-Based Detection System for Protein S K196E Mutation, a Genetic Risk Factor for Venous Thromboembolism

PLoS ONE ◽  
2015 ◽  
Vol 10 (7) ◽  
pp. e0133196 ◽  
Author(s):  
Keiko Maruyama ◽  
Masashi Akiyama ◽  
Koichi Kokame ◽  
Akiko Sekiya ◽  
Eriko Morishita ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Genetic Risk ◽  
Detection System ◽  
Protein S ◽  
Genetic Risk Factor

scholarly journals Prothrombin Arg541Trp Mutation Leads to Defective PC (Protein C) Pathway Activation and Constitutes a Novel Genetic Risk Factor for Venous Thrombosis

2020 ◽  
Vol 40 (2) ◽  
pp. 483-494 ◽  
Author(s):  
Xi Wu ◽  
Jing Dai ◽  
Xiaoqian Xu ◽  
Fang Li ◽  
Lei Li ◽  
...  
Keyword(s):  
Risk Factor ◽  
Family History ◽  
Venous Thrombosis ◽  
Genetic Risk ◽  
Protein C ◽  
Positive Family History ◽  
Genetic Risk Factor ◽  
Procoagulant Activity ◽  
Factor V Leiden Mutation ◽  
History Of

Objective: Defective PC (protein C) pathway predisposes patients to venous thromboembolism (VTE) and is mostly, but not exclusively, attributed to hereditary PC or PS (protein S) deficiencies and activated PC resistance caused by factor V Leiden mutation. Approach and Results: In a patient with acute mesenteric venous thrombosis and positive family history of VTE associated with the impaired PC pathway function determined by thrombin generation test, we identified a novel heterozygous prothrombin mutation p.Arg541Trp. Two more patients with positive family history of VTE carrying the same mutation were identified in a cohort of another 373 unrelated patients, making an overall prevalence of 0.8%. Family investigation revealed 11 individuals in the 3 pedigrees harboring the heterozygous prothrombin p.Arg541Trp mutation, and 8 of them (72%) had experienced episodes of VTE. Functional studies indicated the mutation moderately decreased procoagulant activity of prothrombin and had mild impact on the inactivation of thrombin by its inhibitor antithrombin. However, the amino acid residue substitution significantly compromised PC activation by thrombin, both in the absence and presence of soluble thrombomodulin, and thus rendered prothrombin function procoagulant biased. Conclusions: In summary, the prothrombin p.Arg541Trp mutation constitutes a new genetic risk factor of VTE by impairing function of PC pathway and tilting thrombin’s procoagulant activity over anticoagulant function.

The Prothrombin 20210A Allele Is the Most Prevalent Genetic Risk Factor for Venous Thromboembolism in the Spanish Population

1998 ◽  
Vol 80 (09) ◽  
pp. 366-369 ◽  
Author(s):  
Inma Coll ◽  
Dolors Llobet ◽  
Elisabeth del Río ◽  
Arturo Oliver ◽  
José Mateo ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Genetic Risk ◽  
Recurrent Events ◽  
Geographical Area ◽  
Genetic Risk Factor ◽  
Prothrombin Gene ◽  
Heterozygous Carriers ◽  
Contraceptive Treatment ◽  
Prothrombin 20210A

SummaryWe investigated the prevalence of the new recently reported mutation in the prothrombin gene (20210 A) in a sample of 116 unrelated patients with venous thromboembolism. We found 20 heterozygous carriers (17.2%, CI 95% 10.4-21.1). In comparison, we observed 13 carriers among 201 healthy unmatched controls (6.5%, CI 3.5-10.8). The 20210 A mutation seems to increase the risk of venous thrombosis 3-fold (odds ratio 3.1, 95% CI 1.4-6.6). Considering only patients with a first event (n = 62) the OR was 2.0 (p = 0.18, NS) while those with recurrent events (n = 54) showed an OR of 5.9 (95% CI 2.5-14.4). A majority of heterozygous patients (55%) presented a second thrombophilic factor and 60% of affected females had their first event before 30 years of age, while on oral contraceptive treatment. The prevalence found in this study for healthy people is the highest reported to date. The 20210 A variant appears to be the most prevalent genetic risk factor among patients with thrombosis in our geographical area.

scholarly journals Resistance to activated protein C as an additional genetic risk factor in hereditary deficiency of protein S

Blood ◽  
1995 ◽  
Vol 85 (12) ◽  
pp. 3518-3523 ◽  
Author(s):  
B Zoller ◽  
A Berntsdotter ◽  
P Garcia de Frutos ◽  
B Dahlback
Keyword(s):  
Risk Factor ◽  
Genetic Risk ◽  
Protein C ◽  
Activated Protein C ◽  
Protein S ◽  
Genetic Risk Factor ◽  
Factor V ◽  
Protein S Deficiency ◽  
Apc Resistance ◽  
S Deficiency

Inherited resistance to activated protein C (APC), which is caused by a single point mutation in the gene for factor V, is a common risk factor for thrombosis. In this study, the prevalence of APC resistance in 18 unrelated thrombosis-prone families with inherited protein S deficiency was investigated to determine its role as additional genetic risk factor for thrombosis. In addition, a detailed evaluation of the clinical manifestations in these families was performed. Venous thrombotic events had occurred in 47% of the protein S-deficient patients (64/136) and in 7% of relatives without protein S deficiency (14/191). As estimated from Kaplan-Meier analysis, 50% of protein S-deficient family members and 12% of those without protein S deficiency had had manifestation of venous thromboembolism at the age of 45 years. The age at the first thrombotic event ranged from 10 to 81 years (mean, 32.5 years) and a large intrafamilial and interfamilial variability in expression of thrombotic symptoms was seen. The factor V gene mutation related to APC resistance was present in 6 (38%) of 16 probands available for testing; in total, the mutation was found in 7 (39%) of the 18 families. In family members with combined defects, 72% (13/18) had had thrombosis as compared with 19% (4/21) of those with only protein S deficiency and 19% (4/21) of those with only the factor V mutation. In conclusion, APC resistance was found to be highly prevalent in thrombosis-prone families with protein S deficiency and was an additional genetic risk factor for thrombosis in these families. The results suggest thrombosis-prone families with protein S deficiency often to be affected by yet another genetic defect.

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