title: Factor V G1691A, prothrombin G20210A, and methylenetetrahydrofolate reductase [MTHFR] C677T gene polymorphism in angiographically documented coronary artery disease.
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 micromol/L vs. 16.28 +/- 4.16 micromol/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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Medicine, Arabian Gulf University, Manama, Bahrain. wyalmawi@yahoo.co.uk
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
authors.forename: Ghada
authors.initials: G
authors.lastname: Ameen
authors.forename: Hala
authors.initials: H
authors.lastname: Tamim
authors.forename: Ramzi R
authors.initials: RR
authors.lastname: Finan
authors.forename: Noha
authors.initials: N
authors.lastname: Irani-Hakime
mesh_terms: D000328:Adult; D000368:Aged; D000792:Angiography; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005165:Factor V / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D020138:Hyperhomocysteinemia / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D017720:Molecular Epidemiology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011516:Prothrombin / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)