Ulus Travma Acil Cerrahi Derg. 2009; 15(2): 113-119

Arteriyel trombozlarda faktör V (G1691A), metilentetrahidrofolat redüktaz (C677T) ve protrombin (G20210A) gen mutasyon sýklýðý

Füsun Özmen¹, M. Mahir Özmen², Nejdet Özalp², Nejat Akar^1
1Ankara Üniversitesi Týp Fakültesi Pediatrik Moleküler Genetik Anabilim Dalý, Ankara
²Genel Cerrahi Kliniði, Ankara Numune Eðitim Ve Araþtýrma Hastanesi, Ankara

AMAÇ: Faktör V (FV) [G1691A], metilentetrahidrofolat redüktaz (MTHFR) [C677T] ve protrombin [G20210A] gen mutasyonlarýnýn venöz tromboz riskini artýrdýðý bilinmektedir. Bu mutasyonlarýn, koroner arter hastalýðýndaki sýklýklarý tartýþmalý olmasýna karþýn, tek tek veya birlikte periferik arteriyel tromboz’lardaki (PAT) sýklýklarý bilinmemektedir. Bu çalýþmada, normal saðlýklý bireylerde ve PAT’si olan hastalarda bu mutasyonlarýn sýklýðý araþtýrýldý. GEREÇ-YÖNTEM: Yaþ ortalamasý 31 yýl (daðýlým 20-73) olan 90 (52K) saðlýklý bireyden ve yaþ ortalamasý 63 yýl (daðýlým 16-88) olan 30 (8K) hastadan kan örnekleri alýndý. Klasik proteinaz K / fenol-kloroform yöntemi ile DNA ayrýþtýrýmýný takiben, PCR ürünü spesifik endonükleazlar (Hind III, Hinf I) kullanýlarak kesildi. Elde edilen ürün, agaroz jel elektroforez de yürütülüp etidium bromid ile boyanarak ultraviole ýþýðý altýnda transulliminasyon yöntemi ile görüntülendi. BULGULAR: PAT’si olan hasta grubunda MTHFR ve protrombin gen mutasyon sýklýðý kontrol gurubundan farklý deðildi. Ancak FV G1691A mutasyon sýklýðý anlamlý ölçüde yüksekti. Yine arteriyel trombozlu olgularýn %67’sinde FV ve MTHFR gen mutasyonu birlikte bulunduðu, kontrol gurubu ile karþýlaþtýrýldýðýnda aradaki farkýn anlamlý olduðu ve FV pozitif olgularda MTHFR gen mutasyonu varlýðýnýn riski artýran sinerjistik bir faktör olduðu görüldü. Protrombin gen mutasyonunun tek baþýna ya da diðer gen mutasyonlarý ile birlikte, riski artýran önemli bir faktör olmadýðý görüldü. SONUÇ: PAT’li hastalarda FV ve MTHFR mutasyonlarýnýn artmýþ sýklýðý ve birlikteliðinin, bu hastalarda tromboz oluþumundan sorumlu risk faktörlerinden birisi olabileceði kanaatine varýldý.

Anahtar Kelimeler: Arteriyel tromboz, faktör V; mutasyon; MTHFR; protrombin.

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The prevalence of factor V (G1691A), MTHFR (C677T) and PT (G20210A) gene mutations in arterial thrombosis

Füsun Özmen¹, M. Mahir Özmen², Nejdet Özalp², Nejat Akar^1
1Department Of Pediatric Molecular Genetics, Faculty Of Medicine, Ankara, Turkey
²Department Of Surgery, Ankara Numune Training And Research Hospital, Ankara, Turkey

BACKGROUND: Factor V (FV) [G1691A], methylenetetrahydrofolate reductase (MTHFR) [C677T] and prothrombin (PT) [G20210A] mutations are all well-recognized genetic risk factors for venous thrombosis. Although their prevalence in coronary artery disease has been established through debate, their role in patients with arterial thrombosis remains to be clarified. We investigated the prevalence rates of FV, MTHFR and PT gene mutations in patients with arterial thrombosis and in healthy controls. METHODS: All subjects and controls were from Central Anatolia. Thirty (8F) patients with median (range) age of 63 (16-88) years and 90 (52F) healthy controls with median (range) age of 31 (20-73) years were studied. DNA was extracted using conventional methods (proteinase K/phenol-chloroform) followed by PCR amplification and restriction endonuclease digestion (using Hinf I and Hind III). Digested PCR products were identified using agarose gel electrophoresis and stained with ethidium bromide. RESULTS: The prevalence rates of MTHFR and PT gene mutations were not significantly different between the groups. The prevalence rate of FV mutation was significantly higher in patients with arterial thrombosis. Coinheritance of FV and MTHFR was found in 67% of patients, which was significantly higher in arterial thrombosis, suggesting the MTHFR mutation as a synergistic risk factor for thrombosis in patients with FV mutation. PT gene mutation has no effect on arterial thrombosis. CONCLUSION: The increased prevalence rate and coexistence of both FV and MTHFR found in this group of patients suggest that these mutations might increase the risk of arterial thrombosis.

Keywords: Arterial thrombosis, factor V; gene mutation; MTHFR; prothrombin.

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