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 (14.6percent vs. 15.1percent, p = 0.617) and PRT G20210A (3.1percent vs. 3.0percent; p = 0.936) were similar between patients and controls, respectively. In contrast, the frequency of the MTHFR variant C677T was 71.9percent among patients compared with 45.5percent in controls (p 0.001), of which the T-T genotype was significantly higher among patients (31.3percent) than controls (4.5percent; 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 10.4percent of CAD patients compared 6.9percent 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. © 2004 Kluwer Academic Publishers.