Association between factor XIII single nucleotide polymorphisms and aneurysmal subarachnoid hemorrhage.
OBJECTIVE
Family studies have suggested a role of genetic factors in susceptibility to aneurysmal subarachnoid hemorrhage (aSAH), but the underlying genetic risk factors remain poorly defined. There is an activation of the fibrinolytic system in aSAH, and fibrinolytic markers may be useful in predicting outcome. The authors investigate associations between putative functional variants in genes of importance for fibrinolysis and aSAH and/or outcome following aSAH.


METHODS
One hundred eighty-three patients presenting with aSAH at a neurointensive care unit were consecutively recruited. Two healthy controls per case, matched for age, sex, and geographic region, were randomly recruited. Outcome was assessed after 1 year according to the extended Glasgow Outcome Scale. Single nucleotide polymorphisms (SNPs) in the tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), and factor XIII (FXIII) genes were investigated.


RESULTS
Participants carrying the FXIII 34Leu allele showed an increased risk of aSAH. When adjusting for smoking and hypertension, 2 haplotypes, differing on either the FXIII Val34Leu or the Pro564Leu position, showed an association to aSAH. No significant association was observed for the tPA -7351 C > T, PAI-1 -675 4G > 5G, or TAFI Ala147Thr SNPs. No specific SNP or haplotype was associated with outcome after aSAH, whereas a weak association was observed for a tPA/PAI-1 genotype combination.


CONCLUSIONS
Polymorphisms in the FXIII gene showed association to aSAH. The finding of an increased risk of bleeding in FXIII 34Leu carriers is biologically plausible.
Ladenvall
Claes
C
Institute of Neuroscience and Physiology, Department of Neuroscience and Rehabilitation, the Sahlgrenska Academy at the University of Gothenburg, Sweden.
Csajbok
Ludvig
L
Nylén
Karin
K
Jood
Katarina
K
Nellgård
Bengt
B
Jern
Christina
C
D017542:Aneurysm, Ruptured / Q000150:complications*; D005176:Factor XIII / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013345:Subarachnoid Hemorrhage / Q000235:genetics*
D005176:Factor XIII