The A20210 allele in the prothrombin gene enhances the risk of venous thrombosis in carriers of inherited protein S deficiency.
Sixteen families with inherited protein S deficiency and venous thromboembolism (VT) were screened for the presence of factor V (FV) Leiden mutation and for the G20210A allele in the prothrombin gene. While FV Leiden was not detected in any of the families, protein S deficiency and prothrombin mutation were present in five families. To assess the risk of VT in carriers of the combined defects, a total of 92 members of the 16 families, including propositi, were examined. Thirty subjects were normal, 40 showed protein S deficiency, 10 the prothrombin mutation and 12 showed both abnormalities. When index cases were excluded, thrombosis history were present in 40.7% of protein S-deficient patients, 75% of patients with combined abnormality, one out of the 10 (10%) with prothrombin mutation and only one (3.3%) of the normal subjects. Relatives with combined defects showed the highest incidence rate of VT in comparison with normal relatives (rate ratio = 32.4), those with protein S deficiency an intermediate degree (rate ratio = 15.7), and G20210A relatives the lowest (rate ratio = 3.4). Relatives with combined defects had an increased risk of VT in comparison with relatives with protein S deficiency (incidence rate ratio 2.1; 95% confidence interval, 0.7-5.41; P = 0.1). In conclusion, the presence of the prothrombin mutation seems to increase the risk of VT carriers of protein S deficiency, although additional families are required to fully estimate the magnitude of risk.
Castaman
G
G
Department of Hematology, San Bortolo Hospital, Vicenza, Italy. castaman@hemato.ven.it
Tosetto
A
A
Cappellari
A
A
Ruggeri
M
M
Rodeghiero
F
F
D000328:Adult; D000483:Alleles; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D018455:Protein S Deficiency / Q000235:genetics*; D011516:Prothrombin / Q000235:genetics*; D012306:Risk; D020246:Venous Thrombosis / Q000209:etiology* / Q000235:genetics*
D011516:Prothrombin