Prothrombin and risk of venous thromboembolism, ischemic heart disease and ischemic cerebrovascular disease in the general population.
OBJECTIVE
We tested the hypotheses that Prothrombin G20210A heterozygosity associate with increased risk of venous thromboembolism (VTE), ischemic heart disease (IHD), and ischemic cerebrovascular disease (ICVD) in the general population and re-tested risk of IHD and ICVD in two case-control studies.


METHODS
9231 individuals from the Danish general population were followed for VTE (VTE=DVT+PE), deep venous thrombosis (DVT), pulmonary embolism (PE), IHD, myocardial infarction (MI), ICVD, and ischemic stroke (IS) for a median of 24 years. Case-control studies included 2461 IHD cases and 867 ICVD cases.


RESULTS
In the general population, Prothrombin G20210A heterozygotes had1.3 (95% CI:0.6-2.9) fold risk for VTE, 0.6 (0.2-2.0) for DVT, 1.7(0.6-4.8) for PE, 1.5(1.1-2.1) for IHD, 1.7(1.1-2.7) for MI, 1.1(0.6-1.9) for ICVD, and 1.1(0.5-2.1) for IS compared to non-carriers. Double heterozygotes for Prothrombin G20210A and Factor V Leiden versus double non-carriers had a multifactorially adjusted hazard ratio for IHD of 6.0(2.0-19). In case-control studies, multifactorially adjusted odds ratios for Prothrombin G20210A heterozygotes versus non-carriers were 2.0(1.1-3.4) for IHD, 2.0(1.0-3.8) for MI, 1.4(0.7-3.1) for ICVD, and 2.1(0.8-5.4) for IS.


CONCLUSIONS
Prothrombin G20210A heterozygosity alone and in combination with Factor V Leiden R506Q heterozygosity predicts 1.5 and 6.0 fold risk of IHD compared to non-carriers.
Weischer
Maren
M
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, Copenhagen, Denmark.
Juul
Klaus
K
Zacho
Jeppe
J
Jensen
Gorm B
GB
Steffensen
Rolf
R
Schroeder
Torben V
TV
Tybjaerg-Hansen
Anne
A
Nordestgaard
Børge G
BG
D016022:Case-Control Studies; D002561:Cerebrovascular Disorders / Q000628:therapy*; D003718:Denmark; D006579:Heterozygote; D006801:Humans; D007511:Ischemia / Q000473:pathology*; D009203:Myocardial Infarction / Q000097:blood / Q000628:therapy; D017202:Myocardial Ischemia / Q000628:therapy*; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011516:Prothrombin / Q000235:genetics* / Q000378:metabolism*; D011655:Pulmonary Embolism / Q000097:blood / Q000628:therapy; D012306:Risk; D020521:Stroke / Q000097:blood / Q000628:therapy; D054556:Venous Thromboembolism / Q000097:blood* / Q000628:therapy
D011516:Prothrombin