title: Genotype polymorphisms of GGCX, NQO1, and VKORC1 genes associated with risk susceptibility in patients with large-artery atherosclerotic stroke.
abstract: BACKGROUND
  Gamma-glutamyl carboxylation, a reaction essential for the biosynthesis of vitamin K-dependent coagulation factors, requires the participation of the gamma-glutamyl carboxylase (GGCX), vitamin K epoxide reductase (VKORC1), and NAD(P)H:quinone oxidoreductase (NQO1). We evaluated the role of these genotype polymorphisms in patients with large-artery atherosclerotic stroke.
  
  
  METHODS
  In this hospital-based case-control study, 117 patients who were categorized as having large-artery atherosclerotic stroke and 115 age- and gender-matched controls were recruited. Genotyping determination for the GGCX1 (Gln325Arg), NQO1 (Pro187Ser), and VKORC1 (rs9923231) polymorphisms was performed. The associations of genotype with ischemic stroke (IS) risk were examined.
  
  
  RESULTS
  A higher genotypic frequency of NQO1 C609T was found in the controls than in the patients, manifesting a 0.47-fold risk reduction in IS (95% CI=0.25-0.87). A tendency toward a reduced IS risk was statistically significant in those subjects who carried a greater number of the NQO1, GGCX, and VKORC1 polymorphisms (aOR=0.58, P(trend)=0.005). The synergistic effect of multiple genes on risk reduction was more significant in a subset of patients who were not alcoholics and who were non-smokers (P<0.05).
  
  
  CONCLUSIONS
  Compartmentation of coagulation factor metabolism may account for the preferential role of NQO1, GGCX, and VKORC1 polymorphisms to lower the risk for large-artery atherosclerotic stroke.
authors.affiliation: Neurology Section, Internal Medicine Department, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan.
authors.forename: Hann-Yeh
authors.initials: HY
authors.lastname: Shyu
authors.forename: Chin-Shih
authors.initials: CS
authors.lastname: Fong
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Fu
authors.forename: Jia-Ching
authors.initials: JC
authors.lastname: Shieh
authors.forename: Jiu-Haw
authors.initials: JH
authors.lastname: Yin
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Chang
authors.forename: Hsiao-Wei
authors.initials: HW
authors.lastname: Wang
authors.forename: Chun-Wen
authors.initials: CW
authors.lastname: Cheng
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000201:enzymology / Q000235:genetics*; D019735:Carbon-Carbon Ligases / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000201:enzymology / Q000473:pathology; D006899:Mixed Function Oxygenases / Q000235:genetics*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D064417:Vitamin K Epoxide Reductases
chemical_list: D006899:Mixed Function Oxygenases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase