Résumé
Introduction : La thrombose, une cause majeure de morbi-mortalité, résulte de divers facteurs. Parmi eux, les facteurs de risque génétiques jouent un rôle prépondérant, incluant les mutations du facteur V Leiden, G20210A de la prothrombine et C677T de la méthylènetétrahydrofolate réductase.
Objectifs : Examiner ces mutations chez une population ayant subi un événement thrombotique, en évaluant leur fréquence et leur coexistence ainsi que leur impact sur le risque thrombotique.
Matériel et Méthodes : Il s’agit d’une étude rétrospective analytique menée au sein du laboratoire d'hématologie du Centre Hospitalo-Universitaire sur une période d'un an et demi. Le génotypage des mutations a été effectué par réaction de polymérisation en chaîne en temps réel. L'analyse des données a été réalisée via le logiciel IBM Statistics version 26.
Résultats : Parmi les 50 patients étudiés, 18% présentaient la mutation du facteur V Leiden, associée significativement à la thrombose veineuse profonde (p=0,004). La mutation G20210A de la prothrombine a été détectée chez 6% des patients, principalement lors de thrombose veineuse profonde. Quant à la mutation C677T de la méthylènetétrahydrofolate réductase, elle était présente chez 60% des patients, sans association significative avec un type particulier de thrombose. La présence concomitante des trois mutations a été notée chez 2% des patients.
Conclusion : Cette étude met en lumière l'importance des facteurs génétiques dans la thrombose. Une meilleure compréhension de ces mutations pourrait améliorer la prise en charge et la prévention des événements thrombotiques chez les patients à risque.
Références
Teofilov S, Magic Z, Miljanovic O, Ostojic T, Bulatovic M. Association of prothrombin, FV Leiden and MTHFR gene polymorphisms in the Montenegrin patients with venous thromboembolism. Vojnosanit Pregl. 2021; 78:415-20. DOI: 10.2298/VSP190402086T.
Brill A. Multiple facets of venous thrombosis. Int J Mol Sci. 2021; 22:3853. DOI: 10.3390/ijms22083853.
Padda J, Khalid K, Mohan A, Pokhriyal S, Batra N, Hitawala G, et al. Factor V Leiden G1691A and prothrombin gene G20210A mutations on pregnancy outcome. Cureus. 2021;13: e17185. DOI: 10.7759/cureus.17185.
Cirstoveanu C, Calin N, Heriseanu C, Filip C, Vasile CM, Margarint I, et al. Consistent correlation between MTHFR and vascular thrombosis in neonates: case series and clinical considerations. J Clin Med. 2023; 12:4856. DOI: 10.3390/jcm12144856.
Baccouche H, Belhadj M, Said F, Naceur I, Chakroun A, Houman H, et al. Predicting the risk of recurrent venous thromboembolism: Impact and therapeutic consequences of inherited thrombophilia. J Med Vasc. 2022;47: 125-32. DOI: 10.1016/j.jdmv.2022.08.001.
El Horri M, Kachaa B, Baghdadi M, Kherroubi M. Fréquence des états de thrombophilie biologique dans la maladie thromboembolique veineuse inexpliquée. J Alg Pharm. 2019; 1(2): 18-23.
Chalal N, Demmouche A. Maladie thromboembolique veineuse dans la région de Sidi Bel Abbes, Algérie: fréquence et facteurs de risque. Pan Afr Med J. 2013;16:45. DOI : 10.11604/pamj.2013.16.45.2620.
Ajem A., Slama A., Ben Hadj Slama F, Mehjoub T. Prevalence of factor V Leiden mutation in patients with thrombosis in Tunisia. East Mediterr Health J. 2009; 15:1483-8. https://applications.emro.who.int/emhj/1506/15_6_2009_1483_1488.pdf
Chudej J, Plameňová I. Prothrombin gene 20210A mutation in Slovak population. Vnitr Lek. 2016 ;62 :281-6. https://www.casopisvnitrnilekarstvi.cz/en/artkey/vnl-201604-0010_prothrombin-gene-20210a-mutation-in-slovak-population.php
Yıldız E, Türkmen FM. Factor V Leiden mutation frequency and geographical distribution in Turkish population. J Transl Intern Med. 2020; 8:268-73. DOI: 10.2478/jtim-2020-0040.
de Paula Sabino A, Ribeiro DD, Carvalho Md, Cardoso J, Dusse LM, Fernandes AP. Factor V Leiden and increased risk for arterial thrombotic disease in young Brazilian patients. Blood Coagul Fibrinolysis. 2006; 17:271-5. DOI: 10.1097/01.mbc.0000224846.35001.64.
Montagnana M, Favaloro EJ, Franchini M, Guidi GC, Lippi G. The role of ethnicity, age and gender in venous thromboembolism. J Thromb Thrombolysis. 2010; 29:489-96. DOI: 10.1007/s11239-009-0365-8.
Kreidy R. Factor V-Leiden mutation: a common risk factor for venous thrombosis among Lebanese patients. Thrombosis. 2012; 2012:1-4. DOI: 10.1155/2012/380681.
Al-Otaiby M, Althnayan R, Binmethem A, AlEnezy RB, Alhadlg MA, Alaqeel A, et al. The prevalence of Factor V Leiden (Arg506Gln) mutation in King Khalid University Hospital patients, 2017-2019. Nagoya J Med Sci. 2021 ;83:407-17. DOI : 10.18999/nagjms.83.3.407.
Shafia S, Zargar MH, Khan N, Ahmad R, Shah ZA, Asimi R. High prevalence of factor V Leiden and prothrombin G20101A mutations in Kashmiri patients with venous thromboembolism. Gene. 2018; 654:1-9. DOI: 10.1016/j.gene.2018.02.031.
Raptopoulou A, Michou V, Mourtzi N, Papageorgiou EG, Voyiatzaki C, Tsilivakos V, et al. Large‐scale screening for factor V Leiden (G1691A), prothrombin (G20210A), and MTHFR (C677T) mutations in Greek population. Health Sci Rep. 2022 ;5:e457. DOI : 10.1002/hsr2.457.
Takhviji V, Zibara K, Maleki A, Azizi E, Hommayoun S, Tabatabaei M, et al. A case-control study on factor V Leiden: an independent, gender-dependent risk factor for venous thromboembolism. Thromb J. 2021; 19:74. DOI: 10.1186/s12959-021-00328-0.
Favaloro EJ. Genetic testing for thrombophilia-related genes: observations of testing patterns for factor V Leiden (G1691A) and prothrombin gene "mutation" (G20210A). Semin Thromb Hemost. 2019 ;45 :730-42. DOI : 10.1055/s-0039-1694772.
Ridker PM. Age-specific incidence rates of venous thromboembolism among heterozygous carriers of factor V Leiden mutation. Ann Intern Med. 1997; 126:528. DOI: 10.7326/0003-4819-126-7-199704010-00005.
Press RD, Bauer KA, Kujovich JL, Heit JA. Clinical utility of factor V Leiden (R506Q) testing for the diagnosis and management of thromboembolic disorders. Arch Pathol Lab Med. 2002; 126:1304-18. DOI: 10.5858/2002-126-1304-CUOFVL.
Msalati A, Bashein A, Ghrew M, Khalil I, Sedaa K, Ali A, et al. Association of venous thromboembolism and myocardial infarction with Factor V Leiden and Factor II gene mutations among Libyan patients. Libyan J Med. 2021; 16:1857525. DOI: 10.1080/19932820.2020.1857525.
Elkattawy S, Alyacoub R, Singh KS, Fichadiya H, Kessler W. Prothrombin G20210A gene mutation-induced recurrent deep vein thrombosis and pulmonary embolism: case report and literature review. J Investig Med High Impact Case Rep. 2022; 10:1-8. DOI: 10.1177/23247096211058486.
Padda J, Khalid K, Mohan A, Pokhriyal S, Batra N, Hitawala G, et al. Factor V Leiden G1691A and prothrombin gene G20210A mutations on pregnancy outcome. Cureus. 2021;13: e17185. DOI: 10.7759/cureus.17185.
Linnemann B, Hart C. Laboratory diagnostics in thrombophilia. Hamostaseologie. 2019; 39:49-61. DOI: 10.1055/s-0039-1677840.
Bouaziz-Borgi L, Almawi WY, Mtiraoui N, Nsiri B, Keleshian SH, Kreidy R, et al. Distinct association of factor V-Leiden and prothrombin G20210A mutations with deep venous thrombosis in Tunisia and Lebanon. Am J Hematol. 2006; 81:641-3. DOI: 10.1002/ajh.20582.
Wilcken B. Geographical and ethnic variation of the 677C>T allele of 5,10 methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas world wide. J Med Genet. 2003; 40:619-25. DOI: 10.1136/jmg.40.8.619.
Ben Salem-Berrabah O, Fekih-Mrissa N, N'Siri B, Ben Hamida A, Benammar-Elgaaied A, Gritli N, et al. Thrombophilic polymorphisms - factor V Leiden G1691A, prothrombin G20210A and MTHFR C677T - in Tunisian patients with cerebral venous thrombosis. J Clin Neurosci. 2012; 19:1326-7. DOI: 10.1016/j.jocn.2011.11.029.
Zheng Y, Tong J, Do X, Pu X, Zhou B. Prevalence of methylene-tetrahydrofolate reductase C677T and its association with arterial and venous thrombosis in the Chinese population. Br J Haematol. 2000; 109:870-4. DOI: 10.1046/j.1365-2141.2000.02112.x.
Egin ME, Çeli̇k ZB, Kervan Ü, Karahan M, Tatar A. Investigation of the frequency of thrombophilic gene mutations in patients with venous thromboembolism in eastern Turkey. Genel Tıp Derg. 2023; 33:268-73. DOI: 10.54005/geneltip.1196430.
Gogu AE, Jianu DC, Dumitrascu V, Ples H, Stroe AZ, Docu Axelerad D, et al. MTHFR gene polymorphisms and cardiovascular risk factors, clinical-imagistic features and outcome in cerebral venous sinus thrombosis. Brain Sci. 2020; 11:23.
Şenol S. Methylenetetrahydrofolate reductase polymorphisms in acute deep vein thrombosis. Turk J Vasc Surg. 2019; 28:69-72. DOI: 10.3390/brainsci11010023.
Gao M, Feng N, Zhang M, Ti X, Zuo X. Meta-analysis of the relationship between methylenetetrahydrofolate reductase C677T and A1298C polymorphism and venous thromboembolism in the Caucasian and Asian. Biosci Rep. 2020;40: BSR20200860. DOI: 10.1042/BSR20200860.
Şişli E, Oto Ö. The influence of thrombophilic gene mutation on recurrence of venous thromboembolism: a retrospective cross-sectional study. Osman J Med. 2019; 41:72-80. DOI: 10.20515/otd.435819.
Ce travail est disponible sous la licence Creative Commons Attribution 4.0 International .
(c) Tous droits réservés Rihem Mezrigui, Saoussen Chouchene, Anis Krifa, Achref Chammakhi, Rania Elaissi, Mouna Sassi, Linda Khefacha, Mohsen Hassine 2025