Bite-Sized Genomics

Bite-Sized Genomics: F5 Leiden Mutation

Overview

The F5 Leiden mutation (rs6025) is a rare variant in the human factor V (F5) gene. Individuals with this mutation produce a different version of this protein, which is called Factor V Leiden. The arginine-to-glutamine substitution at position 506 in the coding region renders the encoded protein resistant to the endogenous anticoagulant signal (Activated Protein C). This resistance results in a hypercoagulable state and increased risk of thrombosis.

Clinical Implications

The F5 Leiden mutation is the most common heritable clotting disorder and primarily affects people of European and American ancestry. Since this condition primarily affects venous clotting, patients have an increased risk for venous thromboembolism (VTE). The homozygous genotype (A;A) has been associated with an 11.4 times higher risk of thrombosis, while the heterozygous genotype (A;G) has been associated with a 3.5-4.4 times higher risk of thrombosis.

Interventions

Presently, there is no intervention or treatment that has been found to prevent or cure the condition. Anticoagulant therapy is generally prescribed for those who have had a previous thrombotic event or where there is a greater chance of the development of a future thrombotic event (e.g., surgery, pregnancy, serious illness, etc.). Lifestyle interventions such as maintaining healthy weight, getting regular physical activity, smoking cessation, and avoiding sitting for extended periods of time (during long car rides or flights) may help lessen the occurrence of blood clots.

Some research has found potential benefit of vitamin E in those with this condition.  A large randomized, placebo-controlled study (The Women’s Health Study) that involved 39,867 women looked at the effect of 600 IU of natural vitamin E in those who had an increased risk of developing VTE.  Researchers found that supplementation with vitamin E may reduce the risk of VTE in women, particularly in those with a previous history or genetic predisposition (e.g., factor V Leiden, G20210A prothrombin, and 677C>T MTHFR polymorphisms).  Further research is warranted to investigate the benefits of vitamin E in those at risk of VTE with the factor V polymorphism.   

For further reading:

NIH Genetics Home Reference: https://ghr.nlm.nih.gov/condition/factor-v-leiden-thrombophilia

References

De Stefano V, Leone G. Haematologica. 1995 Jul-Aug;80(4):344-56.

Delluc et al. Thromb Haemost. 2010 Jun;103(6):1161-9.

Glynn RJ, et al. Circulation. 2007 Sep 25;116(13):1497-503.

Heit JA, et al. J Thromb Haemost. 2012 Aug;10(8):1521-31.

Klarin D, et al. Circ Cardiovasc Genet. 2017 Apr;10(2).

Manjunatha P, et al. Global J of Med Res. 2015 Nov; 15(4):5-8.

Rinde LB, et al. J Thromb Haemost. 2019 May;17(5):749-758.

Severinsen MT, et al. Br J Haematol. 2010 Apr;149(2):273-9.

Simone B, et al. Eur J Epidemiol. 2013 Aug;28(8):621-47.

van Hylckama Vlieg, et al. Circ Cardiovasc Genet. 2014 Dec;7(6):806-13. 

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