title: G20210A mutation in the prothrombin gene and the risk of recurrent venous thromboembolism.
abstract: OBJECTIVE
  The study was done to determine whether the G20210A mutation in the prothrombin gene increases the risk of recurrent venous thromboembolism (VTE), both alone and in combination with factor V Leiden.
  
  
  BACKGROUND
  Several inherited defects of coagulation are associated with increased risk of first VTE, including a recently identified G20210A mutation in the prothrombin gene. However, whether the presence of this mutation confers an increased risk of recurrent venous thromboembolism is controversial.
  
  
  METHODS
  A total of 218 men with incident venous thromboembolism were genotyped for the prothrombin mutation and for factor V Leiden and were followed prospectively for recurrent VTE over a follow-up period of 7.3 years.
  
  
  RESULTS
  A total of 29 men (13.3%) suffered recurrent VTE. Five of the 14 carriers of the prothrombin mutation developed recurrent VTE (35.7%; incidence rate = 8.70 per 100 person-years), while 24 of 204 individuals who did not carry the prothrombin mutation developed recurrent VTE (11.8%; incidence rate = 1.76 per 100 person-years). Thus, presence of the G20210A mutation was associated with an approximate fivefold increased risk for recurrent VTE (crude relative risk [RR] 4.93; 95% confidence interval [CI] 1.9-12.9; p = 0.001; age-, smoking-, and body mass index-adjusted RR 5.28; 95% CI 2.0-14.0; p = 0.001). In these data, recurrence rates were similar among those with an isolated mutation in the prothrombin gene (18.2%) as compared to those with an isolated factor V Leiden mutation (19.2%). However, all three study participants who carried both mutations (100%) suffered a recurrent event during follow-up.
  
  
  CONCLUSIONS
  In a prospective evaluation of 218 men, the presence ofprothrombin mutation was associated with a significantly increased risk of recurrent VTE, particularly among those who co-inherited factor V Leiden.
authors.affiliation: Leducq Center for Molecular and Genetic Epidemiology of Cardiovascular Disorders, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Miles
authors.forename: J P
authors.initials: JP
authors.lastname: Miletich
authors.forename: S Z
authors.initials: SZ
authors.lastname: Goldhaber
authors.forename: C H
authors.initials: CH
authors.lastname: Hennekens
authors.forename: P M
authors.initials: PM
authors.lastname: Ridker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005165:Factor V / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011516:Prothrombin / Q000235:genetics*; D012008:Recurrence; D012307:Risk Factors; D013923:Thromboembolism / Q000235:genetics*; D019851:Thrombophilia / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin