Factor V Arg³⁰⁶ → Gly Mutation Is not Associated with Activated Protein C Resistance and Is rare in Taiwanese Chinese

Summary

Polymerase chain reaction amplification followed by BstOI enzyme digestion and DNA sequencing was employed to detect the mutation of factor V gene. The subjects consisted of 105 venous thrombophilic patients and 183 healthy controls. Only one patient was found to have factor V Arg³⁰⁶ → Gly mutation, his elder son also had an identical mutation. None of the healthy subjects studied had Arg³⁰⁶ → Thr mutation. The rare event of factor V Arg³⁰⁶ → Gly mutation in patients and controls suggest that this mutation is not associated with increased risk of venous thrombosis. Conventional, modified and extended activated protein C (APC) resistance assays in this patient and his family members clearly showed that factor V Arg³⁰⁶ → Gly mutation is not associated with APC resistance (APC sensitivity ratio <2). In conclusion, factor V Arg³⁰⁶ → Gly mutation is rare in Taiwanese Chinese and not associated with APC resistance, it is possibly not a risk factor for venous thrombophilic thrombosis.

Key words

Factor V - factor V Arg³⁰⁶ - factor V Gly³⁰⁶ - venous thrombophilia - Taiwanese Chinese

• References

• 1 Kalafatis M, Bertina RM, Rand MD, Mann K. Characterization of molecular defect in the FVR506Q. J Biol Chem 1995; 270: 4053-7.
• 2 Kalafatis M, Rand M, Mann K. The mechanism of inactivation of human factor V and human factor Va by activated protein C. J Biol Chem 1994; 269: 31869-80.
• 3 Griffin JH, Evatt B, Wideman G, Fernandez JA. Anticoagulant protein C pathway defective in majority of thrombophilic patients. Blood 1993; 82: 1989-93.
• 4 Halbayer WM, Haushoffer A, Schon R, Fischer M. The prevalence of poor anticoagulant response to activated protein C (APC resistance) among patients suffering from stroke or venous thrombosis and among healthy subjects. Blood Coagul Fibrinol 1994; 5: 51-7.
• 5 Koster T, Rosendaal FR, de Ronde H, Briet E, Vandenbroucke JP, Bertina RM. Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study. Lancet 1993; 342: 1503-6.
• 6 Svensson PJ, Dahlbäck B. Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 1994; 330: 517-22.
• 7 Chan LC, Bourke C, Lam CK, Brookes S, Liu HW, Jenkins V, Pasi J. Lack of activated protein C resistance in healthy Hong Kong Chinese blood donors-Correlation with absence of Arg⁵⁰⁶ → Gln mutation of factor V gene [letter]. Thromb Haemost 1996; 75: 522-3.
• 8 Shen MC, Lin JS, Tsay W. High prevalence of antithrombin III, protein C and protein S deficiency, but no factor V Leiden mutation in venous thrombophilic Chinese patients in Taiwan. Thromb Res 1997; 87: 377-85.
• 9 Williamson D, Brown K, Ludington R, Baglin C, Baglin T. Factor V Cambridge: A new mutation (Arg³⁰⁶γ Thr) associated with resistance to activated protein C. Blood 1998; 91: 1140-4.
• 10 Chan WP, Lee CK, Kwong YL, Lam CK, Liang R. A novel mutation of Arg³⁰⁶ of factor V gene in Hong Kong Chinese. Blood 1998; 91: 1135-9.
• 11 Dahlbäck B, Carlsson M, Svensson P. Familial thrombophilia due to a previous unrecognized mechanism characterize by poor anticoagulant response to activated protein C: Prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA 1993; 90: 1004-8.
• 12 Kirschbaum NE, Foster PA. The polymerase chain reaction with sequence specific primers for the detection of factor V mutation associated with activated protein C resistance. Thromb Haemost 1995; 74: 874-8.
• 13 Franco RF, Elion J, Tavella MH, Santos SEB, Zago MA. The prevalence of factor V Arg³⁰⁶→ Thr (factor V Cambridge) and factor V Arg³⁰⁶→ Gly mutation in different human populations. Thromb Haemost 1999; 81: 312-3.
• 14 Franco RF, Maffei FH, Lourenco D, Morelli V, Thomazini IA, Piccinato CE, Tavella MH, Zago MA. Factor V Arg³⁰⁶ [arrow right] Thr (factor V Cambridge) and factor V Arg³⁰⁶ [arrow right] Gly mutation in venous thrombotic disease. Brit J Haemat 1998; 103: 888-90.
• 15 Aparicio C, Dahlbäck B. Molecular mechanisms of activated protein C resistance. Biochem J 1996; 313: 467-72.
• 16 Griffin J, Heeb J, Kojima Y, Fernandez J, Kojima K, Hackeng T, Greengard J. Activated protein C resistance: Molecular mechanisms. Thromb Haemost 1995; 74: 444-8.
• 17 Thorelli E, Kaufman RJ, Dahlbäck B. Cleavage of factor V at Arg506 by activated protein C and the expression of anticoagulant activity of factor V. Blood 1999; 93: 2552-8.