title: A case control study on the contribution of factor V-Leiden, prothrombin G20210A, and MTHFR C677T mutations to the genetic susceptibility of deep venous thrombosis.
abstract: BACKGROUND
  Insofar as the inherited prothrombotic single nucleotide polymorphisms (SNPs) factor V G1691A (FV-Leiden), prothrombin (PRT) G20210A, and methylenetetrahydrofolate reductase (MTHFR), C677T are inherited risk factors of venous thromboembolism (VTE), the aim of this study was to determine the prevalence of single and combined SNPs in 198 patients with documented deep venous thrombosis (DVT), and 697 control subjects, and to estimate the associated risks.
  
  
  METHODS
  Factor V-Leiden, PRT G20210A, and MTHFR C677T were analyzed by PCR and restriction fragment length polymorphism (RFLP).
  
  
  RESULTS
  The prevalence of the heterozygote and homozygous variants for FV-Leiden (52.02 vs. 14.78%, RR 6.28), PRT G20210A (19.2 vs. 3.6%; RR 6.38), and to a lesser extent the T/T genotype of MTHFR C677T (20.71 vs. 11.0%; RR 1.49) were higher among DVT patients vs. controls, respectively. Two or more SNPs were detected in 90 of 198 patients (45.5%) and in 60 of 697 controls (8.6%), with odds ratios of 16.754 for joint occurrence of FV-Leiden and PRT G20210A, 10.471 for FV-Leiden and MTHFR C677T, and 6.283 for PRT G20210A SNPs and MTHFR 677T/T. Logistic regression analysis showed a further increased odds for FV-Leiden in combination with PRT G20210A (85.198) or homozygous MTHFR C677T (81.133), and to a lesser extent for PRT G20210A in combination with homozygous MTHFR C677T (20.812).
  
  
  CONCLUSIONS
  This indicates that FV-Leiden and PRT G20210A, more than MTHFR C677T, are important risk factors for DVT, and that the presence of more than one prothrombotic SNPs was associated with a significant risk of DVT.
authors.affiliation: Al-Jawhara Center for Molecular Medicine, Genetics, and Inherited Diseases, Arabian Gulf University, Manama, Bahrain. wyalmawi@yahoo.co.uk
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
authors.forename: Hala
authors.initials: H
authors.lastname: Tamim
authors.forename: Raghid
authors.initials: R
authors.lastname: Kreidy
authors.forename: Georgina
authors.initials: G
authors.lastname: Timson
authors.forename: Elias
authors.initials: E
authors.lastname: Rahal
authors.forename: Malak
authors.initials: M
authors.lastname: Nabulsi
authors.forename: Ramzi R
authors.initials: RR
authors.lastname: Finan
authors.forename: Noha
authors.initials: N
authors.lastname: Irani-Hakime
mesh_terms: D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns; D015810:Linkage Disequilibrium; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D017720:Molecular Epidemiology; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011516:Prothrombin / Q000235:genetics; D018570:Risk Assessment; D019851:Thrombophilia / Q000150:complications / Q000235:genetics*; D020246:Venous Thrombosis / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)