Prothrombin A19911G polymorphism and the risk of venous thromboembolism.
BACKGROUND
The A > G polymorphism at position 19911 of the prothrombin gene is associated with increased plasma prothrombin levels but its role as a risk factor for venous thromboembolism (VTE) is not established.


OBJECTIVE
To investigate the role of prothrombin 19911 A > G polymorphism in the risk of VTE in patients with heterozygous prothrombin 20210GA or factor (F) V Leiden and in those without thrombophilia.


METHODS
Case-control study of 793 patients with prothrombin 20210 GA (n = 167) or FV Leiden (n = 198), and without thrombophilia (n = 428), and of 795 healthy individuals with the corresponding coagulation profile, investigated for the presence of prothrombin 19911 A > G. Plasma prothrombin levels were measured in 342 individuals.


RESULTS
Prothrombin 19911 A > G did not increase the risk of VTE in carriers of prothrombin 20210 GA [odds ratio (OR) 1.2, 95% CI (95% CI) 0.8-1.8] but significantly increased the risk in carriers of FV Leiden (OR 2.1, 95% CI 1.3-3.4) and in patients without thrombophilia (OR 1.5, 95% CI 1.0-2.2). Higher plasma prothrombin levels in carriers of prothrombin 19911 A > G polymorphism than in non-carriers were found among individuals without thrombophilia (P =0.05) and with FV Leiden (P = 0.07), but not in carriers of prothrombin 20210 GA (P = 0.2).


CONCLUSIONS
Prothrombin 19911 A > G polymorphism was independently associated with a 1.5-fold increased risk of VTE and increased 2-fold the risk of VTE associated with FV Leiden, both increases statistically significant. No effect was observed in carriers of prothrombin 20210 GA, perhaps because this polymorphism has a stronger influence on plasma prothrombin levels than the prothrombin 19911 polymorphism.
Martinelli
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I
Department of Internal Medicine and Medical Specialties, A. Bianchi Bonomi Haemophilia and Thrombosis Center, University of Milan, and IRCCS Ospedale Maggiore Policlinico, Mangiagalli and Regina Elena Foundation, Milan, Italy. martin@policlinico.mi.it
Battaglioli
T
T
Tosetto
A
A
Legnani
C
C
Sottile
L
L
Ghiotto
R
R
Mannucci
P M
PM
D000225:Adenine; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006147:Guanine; D006579:Heterozygote; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011516:Prothrombin / Q000235:genetics* / Q000378:metabolism; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood / Q000235:genetics*; D019851:Thrombophilia / Q000097:blood / Q000235:genetics; D020246:Venous Thrombosis / Q000097:blood / Q000235:genetics*
C095381:factor V Leiden; D006147:Guanine; D005165:Factor V; D011516:Prothrombin; D000225:Adenine