Risk of cerebral venous thrombosis and novel gene polymorphisms of the coagulation and fibrinolytic systems.
OBJECTIVE
Genetic thrombophilic conditions such as those associated with Factor V Leiden (FVL) and the prothrombin mutant (PT G20210A) have been identified as risk factors for cerebral venous thrombosis (CVT). Recently, a single nucleotide polymorphism (SNP) of the thrombin activatable fibrinolysis inhibitor (TAFI G-438A) has been shown to be associated with lower TAFI levels and to decrease the risk for peripheral venous thrombosis. Furthermore, a protective role in juvenile stroke was shown for a SNP of the vitamin K dependent protein Z (PZ Intron F G79A) which is linked with low PZ levels.


METHODS
In 77 consecutive patients with CVT and in 203 randomly selected population controls from the same region of Southern Germany, we investigated the following functional SNPs using PCR and restriction fragment analysis techniques: TAFI G-438A, PZ Intron F G79A, FVL and PT G20210A.


RESULTS
The prevalence of FVL tended to be higher (OR 2.08, 95 % CI 0.91-4.75, p = 0.06) and that of PT G20210A (OR 4.57, 95 % CI 1.45-14.44, p = 0.007) was significantly higher in patients with CVT than in controls. The A-allele frequency of the TAFI G-438A polymorphism did not significantly differ between patients (21.3 %) and controls (26.9%; OR 0.71, 95 % CI 0.45-1.12; p = 0.17). For the PZ G79A SNP, the frequency of the A-allele was 19.5% in CVT and 24.6% in controls (OR 0.77, 95 % CI 0.49-1.21; p = 0.31).


CONCLUSIONS
In this large series of CVT patients, a positive association with established thrombophilic risk factors FVL and especially the PT G20210A mutation was confirmed. In contrast, our study found no significant association of CVT with SNPs of the TAFI and the PZ genes. Other than testing for FVL and the PT G20210A mutation, exploration of these potential thrombophilic variants seems to be of limited value in the investigation of CVT.
Lichy
Christoph
C
Dept. of Neurology, University of Heidelberg, INF 400, 69120 Heidelberg, Germany. christoph_lichy@med.uni-heidelberg.de
Dong-Si
Tuan
T
Reuner
Karl
K
Genius
Just
J
Rickmann
Henning
H
Hampe
Toni
T
Dolan
Tarah
T
Stoll
Felix
F
Grau
Armin
A
D000293:Adolescent; D000328:Adult; D001798:Blood Proteins / Q000145:classification / Q000235:genetics*; D025901:Carboxypeptidase B2 / Q000235:genetics; D016022:Case-Control Studies; D018672:Community Health Planning / Q000379:methods; D004252:DNA Mutational Analysis; D005165:Factor V / Q000235:genetics; D005260:Female; D006801:Humans; D020767:Intracranial Thrombosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011516:Prothrombin / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012306:Risk; D018709:Statistics, Nonparametric; D020246:Venous Thrombosis / Q000235:genetics*
D001798:Blood Proteins; D012333:RNA, Messenger; C095381:factor V Leiden; C026080:plasma protein Z; D005165:Factor V; D011516:Prothrombin; D025901:Carboxypeptidase B2