Fibrinogen Aα Thr312Ala polymorphism specifically contributes to chronic thromboembolic pulmonary hypertension by increasing fibrin resistance
Authors: Yuan Lin
Yuan-Hua Yang
Lan Zhao
Su-Qiao Yang
Chen Wang
Jie Liu
Yan Liang
Wei-Juan Zhang
Jun Wang
Ji-Feng Li
Zhen-Guo Zhai
Hui-Li Gan
Na Cui
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Polymorphisms; chronic thromboembolic pulmonary hypertension; pulmonary thromboembolism; fibrin resistance; fibrinogen Aα Thr312Ala
Affiliations: Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, PR China.

Abstract:  Background: 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. Methods: 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). Results: 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. Conclusions: 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. 

Retracted: No

PubPeer comments:
 Figure 1 and Figure 3 showed identical gel figures, which belong to two independent experiments. Could the authors please explain? ![file] ![file] , 
 I am the co-author of this artical.Thank you for your question. The patient shown in Figure 1 and Figure 3 is the same CTEPH patient whose genotype is AG, which is the representative of both CTPEH disease and AG genotype as the results are highly matched. Figure 1 is intended to show the difference between normal control, PTE patients, and CTEPH patients. Figure 3 is intended to show the difference between different genotypes of CTEPH patients. AA, AG, and GG represent three different genotypes of CTEPH patients. , 
 This is Ji-Feng Li, the first author of this paper. Thank you for your question. The patient shown in Figure 1 and Figure 3 is the same CTEPH patient whose genotype is AG, which is the representative of both CTPEH disease and AG genotype as the results are highly matched. Figure 1 is intended to show the difference between normal control, PTE patients, and CTEPH patients. Figure 3 is intended to show the difference between different genotypes of CTEPH patients. AA, AG, and GG represent three different genotypes of CTEPH patients. Thank you again. ,