A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis
Case-control study reveals a prothrombin 3'-UTR mutation increases venous thrombosis risk and prothrombin levels, indicating a common genetic thrombophilia factor.
Key Points
To evaluate the prothrombin gene for mutations in patients with familial venous thrombophilia and quantify its association with plasma prothrombin levels and venous thrombosis risk.
Sequenced all exons, 5'-UTR, and 3'-UTR of the prothrombin gene via polymerase chain reaction and direct sequencing in 28 probands with familial thrombophilia and 100 healthy controls.
Assessed allele frequency, plasma prothrombin concentrations, and thrombosis risk in a population-based case-control study.
Identified a G-to-A transition at position 20210 in the 3'-UTR, present in 18% of probands compared with 1% of healthy controls.
The 20210 A allele showed a 1.2% population frequency (95% CI, 0.5% to 1.8%) and increased venous thrombosis risk nearly threefold (OR, 2.8; 95% CI, 1.4 to 5.6).
87% of individuals carrying the 20210 A allele had plasma prothrombin in the highest quartile (> 1.15 U/mL), which independently served as a thrombosis risk factor.