Molecular Analysis of Prothrombotic Gene Variants in Venous Thrombosis: A Potential Role for Sex and Thrombotic Localization

被引:7
作者
Cernera, Gustavo [1 ,2 ]
Di Minno, Alessandro [2 ,3 ]
Amato, Felice [1 ,2 ]
Elce, Ausilia [2 ,4 ]
Liguori, Renato [1 ,2 ]
Bruzzese, Dario [5 ]
Di Lullo, Antonella Miriam [2 ,6 ]
Castaldo, Giuseppe [1 ,2 ]
Zarrilli, Federica [1 ,2 ]
Comegna, Marika [1 ,2 ]
机构
[1] Univ Napoli Federico II, Dipartimento Med Mol & Biotecnol Med, I-80131 Naples, Italy
[2] CEINGE Biotecnol Avanzate, I-80131 Naples, Italy
[3] Univ Napoli Federico II, Dipartimento Farm, I-80131 Naples, Italy
[4] Univ Telemat Pegaso, I-80143 Naples, Italy
[5] Univ Napoli Federico II, Dipartimento Sanita Pubbl, I-80131 Naples, Italy
[6] Univ Napoli Federico II, Dipartimento Neurosci & Sci Riprod & Odontostomat, I-80131 Naples, Italy
关键词
pulmonary embolism; vein thrombosis; portal vein thrombosis; retinal vein thrombosis; cerebral vein thrombosis; prothrombotic variants; RISK-FACTORS; THROMBOEMBOLISM; POLYMORPHISM; MANAGEMENT;
D O I
10.3390/jcm9041008
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Requests to test for thrombophilia in the clinical context are often not evidence-based. Aim: To define the role of a series of prothrombotic gene variants in a large population of patients with different venous thromboembolic diseases. Methods: We studied Factor V Leiden (FVL), FVR2, FII G20210A, Methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, beta-fibrinogen -455 G>A, FXIII V34L, and HPA-1 L33P variants and PAI-1 4G/5G alleles in 343 male and female patients with deep vein thrombosis (DVT), 164 with pulmonary embolism (PE), 126 with superficial vein thrombosis (SVT), 118 with portal vein thrombosis (PVT), 75 with cerebral vein thrombosis (CVT) and 119 with retinal vein thrombosis (RVT), and compared them with the corresponding variants and alleles in 430 subjects from the general population. Results: About 40% of patients with DVT, PE and SVT had at least one prothrombotic gene variant, such as FVL, FVR2 and FII G20210A, and a statistically significant association with the event was found in males with a history of PE. In patients with a history of PVT or CVT, the FII G20210A variant was more frequent, particularly in females. In contrast, a poor association was found between RVT and prothrombotic risk factors, confirming that local vascular factors have a key role in this thrombotic event. Conclusions: Only FVL, FVR2 and FII G20210A are related to vein thrombotic disease. Other gene variants, often requested for testing in the clinical context, do not differ significantly between cases and controls. Evidence of a sex difference for some variants, once confirmed in larger populations, may help to promote sex-specific prevention of such diseases.
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页数:11
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共 32 条
[1]   Guidance for the management of venous thrombosis in unusual sites [J].
Ageno, Walter ;
Beyer-Westendorf, Jan ;
Garcia, David A. ;
Lazo-Langner, Alejandro ;
McBane, Robert D. ;
Paciaroni, Maurizio .
JOURNAL OF THROMBOSIS AND THROMBOLYSIS, 2016, 41 (01) :129-143
[2]  
Alhenc-Gelas M, 1999, THROMB HAEMOSTASIS, V81, P193
[3]   Thrombophilic Gene Mutations in Relation to Different Manifestations of Venous Thromboembolism: A Single Tertiary Center Study [J].
Bezgin, Tahir ;
Kaymaz, Cihangir ;
Akbal, Ozgur ;
Yilmaz, Fatih ;
Tokgoz, Hacer Ceren ;
Ozdemir, Nihal .
CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS, 2018, 24 (01) :100-106
[4]  
Corral J, 2000, HAEMATOLOGICA, V85, P293
[5]  
Dumic I, 2017, CASE REP GASTROINTES, V2017, DOI 10.1155/2017/5236918
[6]   Polymorphisms in thrombophilic genes are associated with deep venous thromboembolism in an Iranian population [J].
Farajzadeh, Malak ;
Bargahi, Nasrin ;
Zonouzi, Ahmad Poursadegh ;
Farajzadeh, Davoud ;
Pouladi, Nasser .
META GENE, 2014, 2 :505-513
[7]   Molecular Pathophysiology of Portal Hypertension [J].
Fernandez, Mercedes .
HEPATOLOGY, 2015, 61 (04) :1406-1415
[8]   European Stroke Organization guideline for the diagnosis and treatment of cerebral venous thrombosis - endorsed by the European Academy of Neurology [J].
Ferro, J. M. ;
Bousser, M. -G. ;
Canhao, P. ;
Coutinho, J. M. ;
Crassard, I. ;
Dentali, F. ;
di Minno, M. ;
Maino, A. ;
Martinelli, I. ;
Masuhr, F. ;
de Sousa, D. Aguiar ;
Stam, J. .
EUROPEAN JOURNAL OF NEUROLOGY, 2017, 24 (10) :1203-1213
[9]   Retinal vein occlusion: genetic predisposition and systemic risk factors [J].
Giannaki, Kassiani ;
Politou, Marianna ;
Rouvas, Alexandros ;
Merkouri, Efrossyni ;
Travlou, Anthi ;
Theodosiadis, Panayiotis ;
Gialeraki, Argyri .
BLOOD COAGULATION & FIBRINOLYSIS, 2013, 24 (03) :279-283
[10]   Non-genetic and genetic risk factors for adult cerebral venous thrombosis [J].
Green, Mackenzie ;
Styles, Toby ;
Russell, Timothy ;
Sada, Charif ;
Jallow, Ebrima ;
Stewart, Jack ;
Lazariashvili, Otar ;
Lubomirova, Irina ;
Cotlarciuc, Ioana ;
Sharma, Sapna ;
Han, Thang S. ;
Sharma, Pankaj .
THROMBOSIS RESEARCH, 2018, 169 :15-22