Blood Clotting1q24.2

rs6025 - Factor V Leiden - Thrombophilia Risk

Gene: F5 (Factor V)

rs6025 is the Factor V Leiden mutation, the most common inherited cause of abnormal blood clotting (thrombophilia). The A allele creates a variant Factor V protein that is resistant to inactivation by Protein C, leading to a hypercoagulable state.

Genotype Interpretations

GG~95% (European)

Normal Factor V - no increased clotting risk from this variant

GA~5% (European)

Heterozygous carrier - 3-8x increased DVT/PE risk. Important for birth control and surgery decisions

AA~0.02% (European)

Homozygous - ~80x increased DVT/PE risk. Requires anticoagulation management. Avoid estrogen-containing contraceptives

Population Context

Factor V Leiden is almost exclusively found in European populations (~5% carrier frequency). It's extremely rare in African, East Asian, and Indigenous American populations. The mutation is estimated to have arisen ~20,000 years ago in Europe.

Clinical Relevance

Carriers should avoid estrogen-containing contraceptives and HRT, take precautions during long flights/surgery, and inform surgeons and OB/GYNs. Homozygotes typically require lifelong anticoagulation.

Sources

  • [1] Bertina RM et al. (1994) Nature 369:64-7
  • [2] Rosendaal FR et al. (2005) J Thromb Haemost 3:1925-32

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