title: Thrombophilic Gene Mutations in Relation to Different Manifestations of Venous Thromboembolism: A Single Tertiary Center Study.
abstract: BACKGROUND
  Venous thromboembolism (VTE) is a common and potentially lethal disorder that manifests mainly as deep vein thrombosis (DVT) of the extremities or pulmonary embolism (PE) and occurs as a consequence of genetic and environmental risk factors. We aimed to assess the role of inherited thrombophilia as a causative or additive factor in the development of VTE.
  
  
  METHODS
  The study included 310 patients (female: 154; mean age: 52.3 ± 16.9 years) with a first episode of VTE and 289 age- and sex-matched healthy controls. All participants underwent screening for thrombophilia-associated polymorphisms including factor V Leiden (FVL), prothrombin G20210A (PTG), factor V H1299 R (factor V HR2), factor XIII V34 L, β-fibrinogen-455 G>A, plasminogen activator inhibitor-1 4G/5G, human platelet antigen-1 a/b, methylene tetrahydrofolate reductase (MTHFR) C677 T, MTHFR A1298C, angiotensin-converting enzyme I/D, apolipoprotein B R3500Q, and apolipoprotein E (Apo E). In addition, serum homocysteine (Hcy) levels were measured.
  
  
  RESULTS
  In the patient group, 247 (80%) had isolated DVT, 43 (14%) had DVT plus PE, and 20 (6%) had isolated PE. The mean Hcy levels were similar in VTE subgroups and controls. Compared to controls, patients with isolated DVT, DVT plus PE, and isolated PE showed significantly higher frequencies for the following-heterozygous FVL mutation, isolated DVT (28.3%), DVT plus PE (44.2%), isolated PE (50%), controls (8.3%; P < .001); heterozygous PTG mutation, isolated DVT (11.3%), DVT plus PE (20.9%), isolated PE (25%), controls (5.9%; P < .01); Apo E 2/4, isolated DVT (9.7%), DVT plus PE (9.3%), isolated PE (5%), controls (1%; P < .01).The MTHFR A1298C mutation showed a significantly higher frequency in isolated patients with PE than in those with isolated DVT ( P = .006) and in controls ( P = .008). The frequencies of other genetic mutations or polymorphisms showed similar frequencies in all comparisons. In logistic regression analysis, heterozygous FVL mutation was the only independent predictor of VTE (odds ratio: 3.9, 95% confidence interval: 1.3-11.2; P = .012).
  
  
  CONCLUSIONS
  Except than FVL, PTG, and Apo E 2/4 mutations, many of aforementioned thrombophilic factors known to be associated with VTE did not demonstrate any relationship with VTE. Heterozygous mutation of FVL was an independent predictor for VTE.
authors.affiliation: 1 Kartal Koşuyolu Heart and Research Hospital, Cardiology Clinic, Istanbul, Turkey.
authors.forename: Tahir
authors.initials: T
authors.lastname: Bezgin
authors.affiliation: 1 Kartal Koşuyolu Heart and Research Hospital, Cardiology Clinic, Istanbul, Turkey.
authors.forename: Cihangir
authors.initials: C
authors.lastname: Kaymaz
authors.affiliation: 1 Kartal Koşuyolu Heart and Research Hospital, Cardiology Clinic, Istanbul, Turkey.
authors.forename: Özgür
authors.initials: Ö
authors.lastname: Akbal
authors.affiliation: 1 Kartal Koşuyolu Heart and Research Hospital, Cardiology Clinic, Istanbul, Turkey.
authors.forename: Fatih
authors.initials: F
authors.lastname: Yılmaz
authors.affiliation: 1 Kartal Koşuyolu Heart and Research Hospital, Cardiology Clinic, Istanbul, Turkey.
authors.forename: Hacer Ceren
authors.initials: HC
authors.lastname: Tokgöz
authors.affiliation: 1 Kartal Koşuyolu Heart and Research Hospital, Cardiology Clinic, Istanbul, Turkey.
authors.forename: Nihal
authors.initials: N
authors.lastname: Özdemir
mesh_terms: D000328:Adult; D000368:Aged; D016824:Antigens, Human Platelet / Q000097:blood / Q000235:genetics*; D001055:Apolipoproteins B / Q000097:blood / Q000235:genetics*; D001057:Apolipoproteins E / Q000097:blood / Q000235:genetics*; D001779:Blood Coagulation Factors / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D039661:Integrin beta3; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000235:genetics*; D062606:Tertiary Care Centers; D054556:Venous Thromboembolism / Q000097:blood / Q000235:genetics*
chemical_list: D016824:Antigens, Human Platelet; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D001779:Blood Coagulation Factors; C061248:ITGB3 protein, human; D039661:Integrin beta3; C083451:human platelet antigen 1b; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A
keywords: pulmonary embolism; thromboembolism; thrombophilia; venous thrombosis