The association of the beta1-tubulin Q43P polymorphism with intracerebral hemorrhage in men.
OBJECTIVE
Platelets play a fundamental role in hemostasis and alterations of their function can be determinant in the onset of stroke. A polymorphism in beta1-tubulin (TUBB1 Q43P), a protein specifically expressed in the megakaryocytic line, has been described as a protective factor in cardiovascular disease. The potential effect of this variant in the pathogenesis of hemorrhagic stroke has not yet been investigated.


METHODS
We evaluated the role of the TUBB1 Q43P polymorphism and its synergism with other polymorphisms in the risk of developing subarachnoid (SAH) and intracerebral hemorrhage (ICH). We performed the study in 109 patients with SAH, 259 patients with ICH, and 449 subjects from the general population from southern Spain.


RESULTS
No relationship was found between the TUBB1 Q43P polymorphism and SAH. In contrast, this polymorphism significantly increased the risk of ICH in men (OR, 2.78; 95% CI, 1.16-6.63; p=0.021) and was associated with an earlier age of occurrence of an ICH event (p=0.011). Carriers of the TUBB1 Q43P polymorphism displayed lower platelet reactivity towards collagen. A potent synergistic effect was observed in ICH patients carrying the TUBB1 Q43P polymorphism combined with either FVII -323 Del/Ins of a decanucleotide (OR 20.76; 95% CI, 3.57-120.71; p<0.001) or FXIII V34L (OR 7.19; 95% CI, 1.99-25.95; p=0.003).


CONCLUSIONS
This is the first evidence linking the TUBB1 Q43P platelet polymorphism with hemorrhagic stroke in humans. The TUBB1 Q43P polymorphism, by causing a lower reactivity in platelets carrying the variant form of b1-tubulin, protects against thrombotic disorders but increases the risk of ICH in men.
Navarro-Núñez
Leyre
L
Centro Regional de Hemodonación, University of Murcia, Murcia, Spain.
Lozano
María L
ML
Rivera
José
J
Corral
Javier
J
Roldán
Vanessa
V
González-Conejero
Rocío
R
Iniesta
Juan A
JA
Montaner
Joan
J
Vicente
Vicente
V
Martínez
Constantino
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000235:genetics*; D003094:Collagen / Q000494:pharmacology; D015897:Comorbidity; D005167:Factor VII / Q000235:genetics; D005176:Factor XIII / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000648:ultrastructure; D008870:Microtubules / Q000502:physiology; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D012307:Risk Factors; D012737:Sex Factors; D013030:Spain / Q000453:epidemiology; D013345:Subarachnoid Hemorrhage / Q000453:epidemiology / Q000235:genetics; D013927:Thrombosis / Q000235:genetics; D014404:Tubulin / Q000235:genetics* / Q000502:physiology
D014404:Tubulin; D005167:Factor VII; D003094:Collagen; D005176:Factor XIII