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Activated protein C resistance due to a common factor V gene mutation is a major risk factor for venous thrombosis

Zöller, Bengt LU ; Hillarp, Andreas LU ; Berntorp, E LU and Dahlbäck, Björn LU (1997) In Annual Review of Medicine 48. p.45-58
Abstract

Inherited resistance to activated protein C (APC) was recently discovered to be a cause of familial thrombophilia and is now known to be the most common genetic risk factor for venous thrombosis. It is caused by a single point mutation in the gene for factor V, which predicts substitution or arginine (R) at position 506 with a glutamine (Q). Accordingly, the activated form of mutated factor V (FVa:Q506) is more slowly degraded by activated protein C than normal FVa (FVa:R506) is, resulting in hypercoagulability and a lifelong 5- to 10-fold increased risk of venous thrombosis. Previously known inherited hypercoagulable states, i.e. deficiencies of the anticoagulant proteins antithrombin III, protein S, and protein C, are found fewer than... (More)

Inherited resistance to activated protein C (APC) was recently discovered to be a cause of familial thrombophilia and is now known to be the most common genetic risk factor for venous thrombosis. It is caused by a single point mutation in the gene for factor V, which predicts substitution or arginine (R) at position 506 with a glutamine (Q). Accordingly, the activated form of mutated factor V (FVa:Q506) is more slowly degraded by activated protein C than normal FVa (FVa:R506) is, resulting in hypercoagulability and a lifelong 5- to 10-fold increased risk of venous thrombosis. Previously known inherited hypercoagulable states, i.e. deficiencies of the anticoagulant proteins antithrombin III, protein S, and protein C, are found fewer than 10-15% of thrombosis patients in western countries, whereas inherited APC resistance is present in 20-60% of such patients. The FV mutation is common in populations of Caucasian origin, with prevalences ranging from 1-15%, whereas it is not found in certain other ethnic groups such as Japanese and Chinese. The high prevalence of APC resistance, in combination with the availability of simple laboratory tests, will have a profound influence on the development of therapeutic and prophylactic regimens for thrombosis and will, it is hoped, result in a decreased incidence of thromboembolic events.

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publication status
published
subject
keywords
DNA Mutational Analysis, Factor V, Genetic Predisposition to Disease, Genetics, Population, Humans, Oligopeptides, Protein C, Risk Factors, Thrombophlebitis, Journal Article, Review
in
Annual Review of Medicine
volume
48
pages
45 - 58
publisher
Annual Reviews
external identifiers
  • scopus:0031040293
ISSN
0066-4219
DOI
10.1146/annurev.med.48.1.45
language
English
LU publication?
yes
id
2bf55911-9ec4-4ee3-be13-cbb5d203d291
date added to LUP
2017-10-19 16:37:41
date last changed
2017-10-29 05:07:42
@article{2bf55911-9ec4-4ee3-be13-cbb5d203d291,
  abstract     = {<p>Inherited resistance to activated protein C (APC) was recently discovered to be a cause of familial thrombophilia and is now known to be the most common genetic risk factor for venous thrombosis. It is caused by a single point mutation in the gene for factor V, which predicts substitution or arginine (R) at position 506 with a glutamine (Q). Accordingly, the activated form of mutated factor V (FVa:Q506) is more slowly degraded by activated protein C than normal FVa (FVa:R506) is, resulting in hypercoagulability and a lifelong 5- to 10-fold increased risk of venous thrombosis. Previously known inherited hypercoagulable states, i.e. deficiencies of the anticoagulant proteins antithrombin III, protein S, and protein C, are found fewer than 10-15% of thrombosis patients in western countries, whereas inherited APC resistance is present in 20-60% of such patients. The FV mutation is common in populations of Caucasian origin, with prevalences ranging from 1-15%, whereas it is not found in certain other ethnic groups such as Japanese and Chinese. The high prevalence of APC resistance, in combination with the availability of simple laboratory tests, will have a profound influence on the development of therapeutic and prophylactic regimens for thrombosis and will, it is hoped, result in a decreased incidence of thromboembolic events.</p>},
  author       = {Zöller, Bengt and Hillarp, Andreas and Berntorp, E and Dahlbäck, Björn},
  issn         = {0066-4219},
  keyword      = {DNA Mutational Analysis,Factor V,Genetic Predisposition to Disease,Genetics, Population,Humans,Oligopeptides,Protein C,Risk Factors,Thrombophlebitis,Journal Article,Review},
  language     = {eng},
  pages        = {45--58},
  publisher    = {Annual Reviews},
  series       = {Annual Review of Medicine},
  title        = {Activated protein C resistance due to a common factor V gene mutation is a major risk factor for venous thrombosis},
  url          = {http://dx.doi.org/10.1146/annurev.med.48.1.45},
  volume       = {48},
  year         = {1997},
}