title: Genes influencing coagulation and the risk of aneurysmal subarachnoid hemorrhage, and subsequent complications of secondary cerebral ischemia and rebleeding.
abstract: BACKGROUND
  We investigated whether genes influencing coagulation are associated with the occurrence of aneurysmal subarachnoid hemorrhage (SAH) and with secondary cerebral ischemia and rebleeding in patients with aneurysmal SAH.
  
  
  METHODS
  Genotyping for factor V Leiden (G1691A), prothrombin G20210A, methylenetetetrahydrofolate reductase (MTHFR) C677T, factor XIII subunit A Val34Leu, Tyr204Phe and Pro564Leu, and factor XIII subunit B His95Arg was performed in 208 patients with aneurysmal SAH and in 925 controls. Secondary cerebral ischemia occurred in 49 (24%) patients and rebleeding in 28 (14%) during their clinical course of 3 months after the aneurysmal SAH. The risk of aneurysmal SAH was assessed as odds ratio (OR) with 95% confidence interval (95% CI). The risk of secondary cerebral ischemia and rebleeding was assessed as hazard ratio (HR) with 95% CI using Cox regression.
  
  
  RESULTS
  Carriers of the subunit B His95Arg factor XIII polymorphism had an increased risk of aneurysmal SAH with 23% of the patients homozygous or heterozygous for the variant allele compared to 17% of control subjects (OR 1.5, 95% CI 1.0-2.2). For the remaining genetic variants no effect on the risk of aneurysmal SAH could be demonstrated. A clear relation with the risk of secondary cerebral ischemia and of rebleeding could not be established for any of the genetic variants.
  
  
  CONCLUSIONS
  We found that aneurysmal SAH patients are more often carriers of the subunit B His95Arg factor XIII polymorphism compared to controls. This suggests that carriers of the subunit B His95Arg factor XIII polymorphism have an increased risk of aneurysmal SAH. Larger studies should confirm our results. As aneurysmal SAH patients who died soon after admission could not be included in the present study, our results only apply to a population of patients who survived the initial hours after the hemorrhage. For the other studied genetic factors involved in coagulation, no association with the occurrence of aneurysmal SAH or with the occurrence of secondary cerebral ischemia or rebleeding after aneurysmal SAH could be demonstrated.
authors.affiliation: Department of Neurology, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, PO Box 85500, 3500 GA Utrecht, The Netherlands. ij.m.ruigrok@umcutrecht.nl
authors.forename: Ynte M
authors.initials: YM
authors.lastname: Ruigrok
authors.forename: Arjen J C
authors.initials: AJ
authors.lastname: Slooter
authors.forename: Gabriel J E
authors.initials: GJ
authors.lastname: Rinkel
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001798:Blood Proteins / Q000235:genetics; D002545:Brain Ischemia / Q000235:genetics* / Q000503:physiopathology; D020147:Coagulation Protein Disorders / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004252:DNA Mutational Analysis; D005176:Factor XIII / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D055502:Secondary Prevention; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology
chemical_list: D001798:Blood Proteins; D005819:Genetic Markers; D005176:Factor XIII; C054380:factor XIIIb