title: A common polymorphism of the protein Z gene is associated with protein Z plasma levels and with risk of cerebral ischemia in the young.
abstract: OBJECTIVE
  The vitamin K-dependent protein Z (PZ) has been shown to possess anticoagulant as well as procoagulant properties. Plasma levels of PZ show a broad interindividual variation, but it is unknown to which extent this variation is under genetic control. Recent clinical studies revealed contradictory results on the association of PZ plasma levels and the risk of ischemic stroke.
  
  
  METHODS
  We performed a case-control study including 200 patients with cerebral ischemia aged < or =50 years and 199 control subjects from the same South German region. We investigated a possible association of 2 common single nucleotide mutations in the PZ gene with the risk of cerebral ischemia. Furthermore, enzyme-linked immunosorbent assay measurements were done in control subjects without vascular disease to detect a potential association of different genotypes with PZ plasma (antigen) levels.
  
  
  RESULTS
  In patients, the frequency of the A allele of the intron F polymorphism G79A was significantly lower than in controls (15.7% versus 24.4%; odds ratio, 0.58; 95% CI, 0.39 to 0.86; P=0.007; adjusted for age, sex, and conventional risk factors). The G allele of the promoter polymorphism A-13G tended to be less common in patients (4.2% versus 7.0%; adjusted odds ratio, 0.56; 95% CI, 0.28 to 1.13; P=0.105). In 42 control subjects, the A allele of the intron F polymorphism was associated with lower PZ antigen levels (P=0.0032; Spearman correlation coefficient rs=-0.48).
  
  
  CONCLUSIONS
  The A allele of an intron F polymorphism of the PZ gene appears to be a novel protective genetic marker for the risk of cerebral ischemia in young adults. In the context of juvenile stroke, high PZ plasma levels may represent a prothrombotic condition.
authors.affiliation: Department of Neurology, University of Heidelberg, INF 400, 69120 Heidelberg, Germany. christoph_lichy@med.uni-heidelberg.de
authors.forename: C
authors.initials: C
authors.lastname: Lichy
authors.forename: S
authors.initials: S
authors.lastname: Kropp
authors.forename: T
authors.initials: T
authors.lastname: Dong-Si
authors.forename: J
authors.initials: J
authors.lastname: Genius
authors.forename: T
authors.initials: T
authors.lastname: Dolan
authors.forename: T
authors.initials: T
authors.lastname: Hampe
authors.forename: F
authors.initials: F
authors.lastname: Stoll
authors.forename: K
authors.initials: K
authors.lastname: Reuner
authors.forename: C
authors.initials: C
authors.lastname: Grond-Ginsbach
authors.forename: A
authors.initials: A
authors.lastname: Grau
mesh_terms: D000328:Adult; D001798:Blood Proteins / Q000032:analysis* / Q000235:genetics*; D002545:Brain Ischemia / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005165:Factor V / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D011401:Promoter Regions, Genetic; D011516:Prothrombin / Q000235:genetics; D018570:Risk Assessment; D025521:Tumor Suppressor Proteins
chemical_list: D001798:Blood Proteins; D008565:Membrane Proteins; C449281:TMEM158 protein, human; D025521:Tumor Suppressor Proteins; C095381:factor V Leiden; C026080:plasma protein Z; D005165:Factor V; D011516:Prothrombin