The association of prothrombin A19911G polymorphism with plasma prothrombin activity and venous thrombosis: results of the MEGA study, a large population-based case–control study

Y. Chinthammitr, H.L. Vos, F.R. Rosendaal (Corresponding Author), C.J.M. Doggen

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Abstract

Background: Prothrombin (FII) G20210A mutation and elevated plasma prothrombin activity are known risk factors for venous thrombosis. The risk of venous thrombosis among 19911G carriers of the prothrombin A19911G polymorphism has not been extensively investigated.

Objectives and methods: We assessed prothrombin activity, FIIG20210A, and FIIA19911G polymorphisms in a large population-based case–control study, the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis. Four thousand three hundred and sixty-five consecutive patients with a first episode of deep vein thrombosis of the leg or pulmonary embolism were included. The control group (n = 4779) consisted of partners of patients or persons gathered using a random-digit dialing method. We studied the effect of FIIA19911G polymorphism on prothrombin activity and thrombosis risk, also in combination with factor V Leiden.

Results: Among FII20210-GG control subjects, FII19911-GG carriers had 7.1% [95% confidence interval (CI): 5.7–8.5] higher mean prothrombin activity than FII19911-AA carriers and the risk for GG carriers was 1.43-fold increased compared to AA carriers [odds ratio (OR) 1.43; 95% CI: 1.27–1.61]. Among FII20210-GA control carriers, the mean prothrombin activity in both FII19911-AA and -AG carriers was nearly equivalent [131.7% and 133.4%; mean difference (95% CI) = 1.7% (−7.2–10.7)]. Because of genetic linkage, FII19911-GG carriers were very rare on a FII20210-GA background, as only one FII20210A carrier had FII19911-GG. In FII20210-GA carriers, the OR increased from 3.05 (95% CI: 2.17–4.27) in subjects with FII19911-AA to 3.33 (2.28–4.85) in subjects with FII19911-AG, compared to those with FII20210-GG and FII19911-AA.

Conclusions: The FIIA19911G polymorphism is associated with mildly elevated prothrombin activity and is a risk factor for venous thrombosis.
Original languageEnglish
Pages (from-to)2587-2592
JournalJournal of thrombosis and haemostasis
Volume4
Issue number12
DOIs
Publication statusPublished - 2006
Externally publishedYes

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Prothrombin
Venous Thrombosis
Population
Confidence Intervals
Odds Ratio
Genetic Linkage
Pulmonary Embolism
Leg
Thrombosis
Control Groups
Mutation

Keywords

  • IR-77869
  • prothrombin mutations
  • risk factor
  • VENOUS THROMBOSIS

Cite this

@article{06956d29b5c143e69ce1179072758344,
title = "The association of prothrombin A19911G polymorphism with plasma prothrombin activity and venous thrombosis: results of the MEGA study, a large population-based case–control study",
abstract = "Background: Prothrombin (FII) G20210A mutation and elevated plasma prothrombin activity are known risk factors for venous thrombosis. The risk of venous thrombosis among 19911G carriers of the prothrombin A19911G polymorphism has not been extensively investigated.Objectives and methods: We assessed prothrombin activity, FIIG20210A, and FIIA19911G polymorphisms in a large population-based case–control study, the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis. Four thousand three hundred and sixty-five consecutive patients with a first episode of deep vein thrombosis of the leg or pulmonary embolism were included. The control group (n = 4779) consisted of partners of patients or persons gathered using a random-digit dialing method. We studied the effect of FIIA19911G polymorphism on prothrombin activity and thrombosis risk, also in combination with factor V Leiden.Results: Among FII20210-GG control subjects, FII19911-GG carriers had 7.1{\%} [95{\%} confidence interval (CI): 5.7–8.5] higher mean prothrombin activity than FII19911-AA carriers and the risk for GG carriers was 1.43-fold increased compared to AA carriers [odds ratio (OR) 1.43; 95{\%} CI: 1.27–1.61]. Among FII20210-GA control carriers, the mean prothrombin activity in both FII19911-AA and -AG carriers was nearly equivalent [131.7{\%} and 133.4{\%}; mean difference (95{\%} CI) = 1.7{\%} (−7.2–10.7)]. Because of genetic linkage, FII19911-GG carriers were very rare on a FII20210-GA background, as only one FII20210A carrier had FII19911-GG. In FII20210-GA carriers, the OR increased from 3.05 (95{\%} CI: 2.17–4.27) in subjects with FII19911-AA to 3.33 (2.28–4.85) in subjects with FII19911-AG, compared to those with FII20210-GG and FII19911-AA.Conclusions: The FIIA19911G polymorphism is associated with mildly elevated prothrombin activity and is a risk factor for venous thrombosis.",
keywords = "IR-77869, prothrombin mutations, risk factor, VENOUS THROMBOSIS",
author = "Y. Chinthammitr and H.L. Vos and F.R. Rosendaal and C.J.M. Doggen",
year = "2006",
doi = "10.1111/j.1538-7836.2006.02257.x",
language = "English",
volume = "4",
pages = "2587--2592",
journal = "Journal of thrombosis and haemostasis",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "12",

}

The association of prothrombin A19911G polymorphism with plasma prothrombin activity and venous thrombosis : results of the MEGA study, a large population-based case–control study. / Chinthammitr, Y.; Vos, H.L.; Rosendaal, F.R. (Corresponding Author); Doggen, C.J.M.

In: Journal of thrombosis and haemostasis, Vol. 4, No. 12, 2006, p. 2587-2592.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The association of prothrombin A19911G polymorphism with plasma prothrombin activity and venous thrombosis

T2 - results of the MEGA study, a large population-based case–control study

AU - Chinthammitr, Y.

AU - Vos, H.L.

AU - Rosendaal, F.R.

AU - Doggen, C.J.M.

PY - 2006

Y1 - 2006

N2 - Background: Prothrombin (FII) G20210A mutation and elevated plasma prothrombin activity are known risk factors for venous thrombosis. The risk of venous thrombosis among 19911G carriers of the prothrombin A19911G polymorphism has not been extensively investigated.Objectives and methods: We assessed prothrombin activity, FIIG20210A, and FIIA19911G polymorphisms in a large population-based case–control study, the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis. Four thousand three hundred and sixty-five consecutive patients with a first episode of deep vein thrombosis of the leg or pulmonary embolism were included. The control group (n = 4779) consisted of partners of patients or persons gathered using a random-digit dialing method. We studied the effect of FIIA19911G polymorphism on prothrombin activity and thrombosis risk, also in combination with factor V Leiden.Results: Among FII20210-GG control subjects, FII19911-GG carriers had 7.1% [95% confidence interval (CI): 5.7–8.5] higher mean prothrombin activity than FII19911-AA carriers and the risk for GG carriers was 1.43-fold increased compared to AA carriers [odds ratio (OR) 1.43; 95% CI: 1.27–1.61]. Among FII20210-GA control carriers, the mean prothrombin activity in both FII19911-AA and -AG carriers was nearly equivalent [131.7% and 133.4%; mean difference (95% CI) = 1.7% (−7.2–10.7)]. Because of genetic linkage, FII19911-GG carriers were very rare on a FII20210-GA background, as only one FII20210A carrier had FII19911-GG. In FII20210-GA carriers, the OR increased from 3.05 (95% CI: 2.17–4.27) in subjects with FII19911-AA to 3.33 (2.28–4.85) in subjects with FII19911-AG, compared to those with FII20210-GG and FII19911-AA.Conclusions: The FIIA19911G polymorphism is associated with mildly elevated prothrombin activity and is a risk factor for venous thrombosis.

AB - Background: Prothrombin (FII) G20210A mutation and elevated plasma prothrombin activity are known risk factors for venous thrombosis. The risk of venous thrombosis among 19911G carriers of the prothrombin A19911G polymorphism has not been extensively investigated.Objectives and methods: We assessed prothrombin activity, FIIG20210A, and FIIA19911G polymorphisms in a large population-based case–control study, the Multiple Environmental and Genetic Assessment (MEGA) study of risk factors for venous thrombosis. Four thousand three hundred and sixty-five consecutive patients with a first episode of deep vein thrombosis of the leg or pulmonary embolism were included. The control group (n = 4779) consisted of partners of patients or persons gathered using a random-digit dialing method. We studied the effect of FIIA19911G polymorphism on prothrombin activity and thrombosis risk, also in combination with factor V Leiden.Results: Among FII20210-GG control subjects, FII19911-GG carriers had 7.1% [95% confidence interval (CI): 5.7–8.5] higher mean prothrombin activity than FII19911-AA carriers and the risk for GG carriers was 1.43-fold increased compared to AA carriers [odds ratio (OR) 1.43; 95% CI: 1.27–1.61]. Among FII20210-GA control carriers, the mean prothrombin activity in both FII19911-AA and -AG carriers was nearly equivalent [131.7% and 133.4%; mean difference (95% CI) = 1.7% (−7.2–10.7)]. Because of genetic linkage, FII19911-GG carriers were very rare on a FII20210-GA background, as only one FII20210A carrier had FII19911-GG. In FII20210-GA carriers, the OR increased from 3.05 (95% CI: 2.17–4.27) in subjects with FII19911-AA to 3.33 (2.28–4.85) in subjects with FII19911-AG, compared to those with FII20210-GG and FII19911-AA.Conclusions: The FIIA19911G polymorphism is associated with mildly elevated prothrombin activity and is a risk factor for venous thrombosis.

KW - IR-77869

KW - prothrombin mutations

KW - risk factor

KW - VENOUS THROMBOSIS

U2 - 10.1111/j.1538-7836.2006.02257.x

DO - 10.1111/j.1538-7836.2006.02257.x

M3 - Article

VL - 4

SP - 2587

EP - 2592

JO - Journal of thrombosis and haemostasis

JF - Journal of thrombosis and haemostasis

SN - 1538-7933

IS - 12

ER -