(Stroke. 2000;31:1785-c.)
© 2000 American Heart Association, Inc.
Letters to the Editor |
G20210A PRTH Gene Mutation and Other Trombophilic Polymorphisms in Patients With Cerebral Vein Thrombosis
Centro di Coordinamento Regionale per le Emocoagulopatie Clinica Medica, Dipartimento di Medicina Clinica e Sperimentale, Università degli studi di Napoli "Federico II", Napoli, Italy
To the Editor:
The prevalence of some gene polymorphisms associated with inherited thrombophilia and its potential relevance in the ischemic stroke of young women was recently described in Stroke.1 At variance with patients with ischemic stroke, an increased risk of cerebral vein thrombosis (CVT) has been associated with the G20210A prothrombin (PRTH) gene mutation and oral contraceptive drugs. This finding was consistent with those in previous studies.2 3 In another study, a higher-than-normal prevalence of factor V Leiden mutation among CVT patients was reported.4 According to previously described methods,5 we have screened these 2 polymorphisms plus the homozygosity for the thermolabile variant (677TT) of the methylenetetrahydrofolate reductase (MTHFR) gene in 10 consecutive patients (4 men and 6 women; mean age 36.7 years; mean age at first event 35.1 years) referred to our center because of a history of CVT. In all cases, cerebral angiography and/or MRI showed a complete or partial lack of filling of at least 1 sinus. No patient showed venous malformations at the site of thrombosis. Differences in allele frequencies were tested by the Fisher exact test. Five of the 10 CVT patients (50%) were heterozygotes for the G20210A PRTH variant. This frequency was significantly higher (6.3%, P=0.0004) than that in a group of healthy controls subjects matched for sex and age (n=259: 144 women and 115 men; mean±SD age 36.7±12.8 years), from the same ethnic background. The frequency of factor V Leiden and of the MTHFR in patients with CVT were 10% (1/10) and 33.3% (3/10), respectively, ie, twice as much as that found in controls (5.8% [15/259] and 17.4% [45/259], respectively). Two patients had the MTHFR genotype and the G20210A PRTH variant simultaneously; 1 carried the PRTH and the factor V Leiden variants. On the whole, 3 patients (33.3%) showed the coexistence of 2 thrombophilic genes; this was significantly different from the prevalence of the coexistence among healthy subjects (5/259, 1.9%; P=0.0019). Three CVT patients had a family history of venous thromboembolism; all were heterozygous for the G20210A PRTH variant. Four patients showed recurrent venous thromboembolism; among them, 3 carried the G20210A PRTH variant and 2 showed the association of the latter with factor V Leiden or with the MTHFR 677TT genotype. In our female patients, 2 of 6 experienced CVT while using oral contraceptives; none of the polymorphisms was present in both cases.
The coexistence of PRTH and factor V mutation has been strongly associated with juvenile and recurrent venous thromboembolism.6 7 The MTHFR variant increases the risk of deep-vein thrombosis in factor V Leiden carriers.8 Despite the limitations of the sample size, these data confirm the role of the G20210A PRTH variant as a predisposing factor for CVT. Our data also indicate that thrombophilic genes often coexist in patients with CVT. Whether (and the extent towhich) thrombosis at this unusual site reflects a sustained hypercoagulable state needs to be further evaluated.
References
1.
Longstreth WT, Rosendaal FR, Siscovick DS, Vos HL,
Scwartz SM, Psaty BM, Raghunathan TE, Koepsell TD, Reitsma PH. Risk of
stroke in young women and two prothrombotic mutations: factor V Leiden
and prothrombin gene variant (G20210A). Stroke.. 1998;29:577–580.
2.
Martinelli I, Sacchi E, Landi G, Taioli E, Duca F,
Mannucci PM. High risk of cerebral-vein thrombosis in carriers of a
prothrombin gene mutation and in users of oral contraceptives.
N Engl J Med.. 1998;338:1793–1797.
3.
Reuner KH, Ruf A, Grau A, Rickmann H, Stolz E, Juttler
E, Druschky KF, Patscheke H. Prothrombin gene G20210
A
transition is a risk factor for cerebral venous thrombosis.
Stroke.. 1998;29:1765–1769.
4.
Ludemann P, Nabavi DG, Junker R, Wolff E, Papke K,
Buchner H, Assmann G, Ringelstein EB. Factor V Leiden mutation is a
risk factor for cerebral vein thrombosis: a case-control study of 55
patients. Stroke.. 1998;29:2507–2510.
5. Piemontino U, Guiotto G, Rugiada F, Cirillo F, Cerbone AM. Abnormal high frequency of inherited pro-thrombotic condition in subjects with recurrence of venous thrombosis. Thromb Haemost.. 1999;82:1359–1360.[Medline] [Order article via Infotrieve]
6.
De Stefano V, Martinelli I, Mannucci PM, Paciaroni K,
Chiusolo P, Casarelli I, Rossi E, Leone G. The risk of recurrent deep
venous thrombosis among heterozygous carriers of both factor V Leiden
and G20210A prothrombin mutation. N Engl J Med.. 1999;341:801–806.
7. Margaglione M, D’Andrea G, Colaizzo D, Cappucci G, del Popolo A, Brancaccio V, Ciampa A, Grandone E, Di Minno G. Coexistence of factor V Leiden and factor II A20210 mutation and recurrent venous thromboembolism. Thromb Haemost.. 1999;82:1583–1587.[Medline] [Order article via Infotrieve]
8.
Cattaneo M, Tsai MY, Bucciarelli P, Taioli E, Zighetti
ML, Bignell M, Manucci PM. A common mutation in the
methylenetetrahydrofolate reductase
gene (C677T) increases the risk for deep-vein thrombosis in patient
with mutant factor V (Factor V:Q506). Arterioscler
Thromb Vasc Biol.. 1997;17:1662–1666.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||