Factor V Leiden Mutation

Factor V Leiden Mutation

Factor V Leiden is the name of the single base mutation in the gene (referred to as F5) for coagulation Factor V protein molecule. This mutation causes a missense substitution of glutamic acid for an arginine at amino acid 506 or 534 depending on the accepted start-position. Since this is the cleavage site for activated protein C (APC) to inactivate Factor V, this substitution prevents efficient inactivation of factor V (resistance to activated protein C) resulting in an increased tendency to form abnormal blood clots that causes hypercoagulability disorder (Thrombophilia). [1],[2]

Factor V Leiden which is the common inherited form of thrombophilia occurs in 3%-5% of the general population and in 20%-40% of patients with venous thromboembolic disease. The risk of blood clot mainly depends on  if a person inherits one or two copies of the factor V Leiden mutation. Individuals inheriting one copy of the mutation (Heterozygous for the factor V Leiden defect ) have a 5-10 fold increased risk of thrombosis, while people  inheriting two copies of the mutation (homozygous for the factor V Leiden defect), one from each parent, may have up to 50-100 fold increased risk of developing this type of blood clot than wild-type (WT) healthy individuals. [3], [4]

The diagnosis of thrombophilia is mainly run by two methods, a screening test called a coagulation screening test or by genetic testing ( DNA analysis) of the Factor V coding gene ( F5 gene). Screening test is based on the relative resistance of Factor V Leiden to activated protein C (APCR) where two simultaneous tests are applied, one in the presence of activated protein C (APC) and the other in the absence and final determined ratio within two tests signify whether APC is working out or not.  Activated protein C resistance assays (APCR) are quick, automated tests that can be easily performed but however may not distinguish between heterozygous and homozygous with Factor V Leiden which then  may results in overlap between unaffected individuals and individuals heterozygous for Factor  V Leiden.  Since the treatment differ for two genotypes and DNA-based assays are not affected by other factors like pregnancy,  the therapeutic use of anticoagulants,  use of oral contraceptives..etc, it makes the genetic testing highly reliable and desirable for using in the  detection of the factor V Leiden mutation. [5], [6]

Annotated Bibliography

1-Bertina, R.M., et al., Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature, 1994. 369(6475): p. 64-7.

2-Genetic home reference, NIH Resources, Factor V Leiden thrombophilia, August 2010

Herrmann, Koesling, et al., Prevalence of factor V Leiden mutation in various populations. Genet. 3-Epidemiology, 1997. 14(4): p. 403-411.

4-Epidemiology: Rees DC, Cox M, Clegg JB. World distribution of factor V Leiden. Lancet 1995;346:1133–4

5-Charles T. Lutz, Paul A. Foster, et al., Multicenter Evaluation of PCR Methods for the Detection of Factor V Leiden (R506Q) Genotypes, Clin. Chem., Jun 1998; 44: 1356 - 1358.

6-P.C.Cooper, S.M.Rezende, et al., An overview of methods for detection of factor V Leiden and the prothrombin G20210A mutations, International Journal of Laboratory Hematology, October 2007, 29, 153-162