Genotype polymorphisms of GGCX, NQO1, and VKORC1 genes associated with risk susceptibility in patients with large-artery atherosclerotic stroke.
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.
Shyu
Hann-Yeh
HY
Neurology Section, Internal Medicine Department, Armed Forces Taoyuan General Hospital, Taoyuan, Taiwan.
Fong
Chin-Shih
CS
Fu
Yi-Ping
YP
Shieh
Jia-Ching
JC
Yin
Jiu-Haw
JH
Chang
Ching-Yi
CY
Wang
Hsiao-Wei
HW
Cheng
Chun-Wen
CW
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
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