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Factor V G1691A, Prothrombin G20210A, and Methylenetetrahydrofolate Reductase [MTHFR] C677T Gene Polymorphism in Angiographically Documented Coronary Artery Disease

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Abstract

Background: Single point mutations in the genes coding for factor V [G1691A; Leiden], prothrombin [PRT; G20210A], and methylenetetrahydrofolate reductase [MTHFR, C677T] were shown to be major inherited predisposing factors for venous thromboembolism. However, their contribution in the development of coronary artery disease [CAD] remains controversial. The aim of the study was to examine the association of these mutations in CAD.

Methods: A total of 96 patients with angiographically-demonstrated CAD [mean age 55.3 ± 11.3], and 404 healthy subjects [mean age 50.7 ± 8.9] were recruited into the study. Fasting plasma homocysteine was determined by HPLC, and genotype analysis was assessed by PCR-RFLP.

Results: The carrier frequency of factor V-Leiden (14.6% vs. 15.1%, p = 0.617) and PRT G20210A (3.1% vs. 3.0%; p = 0.936) were similar between patients and controls, respectively. In contrast, the frequency of the MTHFR variant C677T was 71.9% among patients compared with 45.5% in controls (p < 0.001), of which the T/T genotype was significantly higher among patients (31.3%) than controls (4.5%; p < 0.001). Significantly higher homocysteine levels were seen among T/T genotype in both groups compared to non-T/T carriers (p < 0.05), and among patients compared with controls (18.47 ± 3.73 μmol/L vs. 16.28 ± 4.16 μmol/L). In addition, the coexistence of MTHFR C677T with FV-Leiden was seen in 10.4% of CAD patients compared 6.9% of controls (p = 0.001).

Conclusion: While results from this study clearly demonstrate a strong association of hyperhomocysteinemia and homozygosity of the MTHFR C677T, but not FV-Leiden or PRT G20210A, mutations with confirmed CAD, they also suggest a potential role for factor V-Leiden in MTHFR C677T carriers.

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Authors and Affiliations

  1. Department of Medicine, Arabian Gulf University, Manama, Bahrain

    Wassim Y. Almawi & Ghada Ameen

  2. Department of Epidemiology and Biostatistics, American University of Beirut, Lebanon

    Hala Tamim

  3. Department of Obstetrics and Gynecology, St. Georges-Orthodox Hospital, Beirut, Lebanon

    Ramzi R. Finan & Noha Irani-Hakime

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Almawi, W.Y., Ameen, G., Tamim, H. et al. Factor V G1691A, Prothrombin G20210A, and Methylenetetrahydrofolate Reductase [MTHFR] C677T Gene Polymorphism in Angiographically Documented Coronary Artery Disease. J Thromb Thrombolysis 17, 199–205 (2004). https://doi.org/10.1023/B:THRO.0000040489.86029.27

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