Thrombosis Research 89 (1998) 249–252 BRIEF COMMUNICATION Factor II 20210 G→A Polymorphism Associated to Factor V Leiden: A Report of Two Thrombophilic Families Domenico Prisco, Anna Maria Gori, Guglielmina Pepe, Rossella Marcucci, Tamara Brunelli, Betti Giusti, Gian Franco Gensini and Rosanna Abbate Istituto di Clinica Medica Generale e Cardiologia, Universita ` di Firenze, Firenze, Italy. (Received 7 November 1997 by Editor M. Cattaneo; revised/accepted 19 December 1997) Key Words: FII polymorphism; FV Leiden; Venous throm- venous thrombosis: APC resistance is present in boembolism 20–60% of venous thrombosis cases [5]. It is caused by a single point mutation in the factor V gene. A number of hereditary disorders, in particular The mutation is common in Europeans (from 1.5% those affecting the physiological anticoag- to 15%) [7] and in North-Americans (from 0.45% ulant systems, have been well established to 5.27%) [7], while it was not found among other as risk factors for venous thromboembolism [1,2]. human groups [6,7]. Based on the age of the first thrombotic episode, its Another new candidate for venous thrombosis is a polymorphism of prothrombin gene which is severity and its prevalence among affected people, localized to chromosome 11. Poort and coworkers this risk is defined as excessive, high, intermediate, [8] found a genetic variant (a G to A transition at or low [3]. The categorization of risks on single gene position 20210) of the prothrombin gene in 18% of disorders is far from being satisfactory, in view of a group of thrombophilic Dutch patients. Recently, the variable manifestations of thrombosis observed Hillarp et al. [9] confirmed the 20210 A allele of in affected family members with identical genotype. the prothrombin gene and suggested this to be an In some instances this heterogeneity could be related important genetic risk factor also among Swedish to variable exposures of affected patients to acquired population; they found the mutation in 7.1% of pa- prothrombotic circumstances such as surgery, preg- tients with history of deep vein thrombosis (DVT) nancy, or use of oral contraceptives, but, in most versus 1.8% of healthy controls. It is unclear how instances, no good explanation could be provided. the genetic variant G→A 20210 predisposes to These observations have led to the hypothesis that, thrombosis. Possibly, prothrombin polymorphism among family members affected by one of the men- determines higher prothrombin concentrations tioned mutant genes, more than one genetic risk that may result in increased thrombin generation. factor might cosegregate and contribute to the We describe two Italian thrombophilic families thrombophilic phenotype [4]. having a combination of mutations: polymorphism In 1993, inherited resistance to activated protein of prothrombin gene plus factor V Leiden. C (APC) was described as a novel risk factor for 1. Materials and Methods Abbreviations: VTE, venous thromboembolism; APC, activated protein C; DVT, deep vein thrombosis; PAI, plasminogen activa- 1.1. Coagulation Assays tor inhibitory activity. Corresponding author: Prof. Domenico Prisco, Clinica Medica Antithrombin (AT) and protein C (PC) activities Generale e Cardiologia, Universita ` di Firenze, Viale Morgagni, 85, 50134 Firenze, Italia. Fax: 39–55–4277608; Tel: 39–55–4277610. were evaluated by automated chromogenic meth- 0049-3848/98 $19.00 + .00  1998 Elsevier Science Ltd. Printed in the USA. All rights reserved. PII S0049-3848(98)00013-9