Fibrinogen Aα Thr312Ala polymorphism specifically contributes to chronic thromboembolic pulmonary hypertension by increasing fibrin resistance

• Published in: PloS one Vol. 8; no. 7; p. e69635
• Main Authors: Li, Ji-Feng, Lin, Yuan, Yang, Yuan-Hua, Gan, Hui-Li, Liang, Yan, Liu, Jie, Yang, Su-Qiao, Zhang, Wei-Juan, Cui, Na, Zhao, Lan, Zhai, Zhen-Guo, Wang, Jun, Wang, Chen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 22.07.2013; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anticoagulants; Biology; Biomarkers; Chronic Disease; Confidence intervals; Critical care; Disease; Embolisms; Female; Fibrin; Fibrin - metabolism; Fibrinogen; Fibrinogen - genetics; Fibrinolysis - genetics; Gene Frequency; Gene polymorphism; Genotype; Genotypes; Health risk assessment; Heart attacks; Hospitals; Humans; Hypertension; Hypertension, Pulmonary - complications; Hypertension, Pulmonary - genetics; Hypertension, Pulmonary - physiopathology; Laboratories; Lysis; Male; Medicine; Middle Aged; Mutation; Physiology; Plasmin; Polymorphism; Polymorphism, Single Nucleotide; Pulmonary arteries; Pulmonary Embolism - complications; Pulmonary embolisms; Pulmonary hypertension; Respiratory diseases; Restriction fragment length polymorphism; Risk factors; Stroke; Thromboembolism; Thrombosis; Young Adult; Beijing China; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0069635

Polymorphisms are associated with chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary thromboembolism (PTE), but no polymorphism specific to CTEPH but not PTE has yet been reported. Fibrin resistance is associated with CTEPH, but the mechanism has not been elucidated. Polymorphisms were analyzed in 101 CTEPH subjects, 102 PTE subjects and 108 healthy controls by Massarray or restriction fragment length polymorphism (RFLP). Plasmin-mediated cleavage of fibrin was characterized in 69 subjects (29 with CTEPH, 21 with PTE and 19 controls). Genotype frequencies and allele frequencies of fibrinogen Aα Thr312Ala were significantly higher in CTEPH subjects than in controls and PTE subjects, while there was no difference between PTE subjects and controls. The odd ratio (OR 2.037) and 95% confidence interval (95% CI, 1.262-3.289) showed that Thr312Ala polymorphism was a risk factor for CTEPH but not PTE. Fibrin from CTEPH subjects was more resistant to lysis than that from PTE subjects and controls. Fibrin resistance was significantly different between Aα Thr312Ala (A/G) genotypes within CTEPH subjects, and the fibrin with GG genotype was more resistant than that with AA and AG genotype. Fibrinogen Aα Thr312Ala (A/G) polymorphism was associated with CTEPH, but not PTE, suggesting that the fibrinogen Aα Thr312Ala polymorphism may act as a potential biomarker in identifying CTEPH from PTE. GG genotype polymorphism contributes to CTEPH through increasing fibrin resistance, implying that PTE subjects with fibrinogen Aα GG genotype may need long-term anticoagulation therapy.