Association of common variants of CYP4A11 and CYP4F2 with stroke in the Han Chinese population.
OBJECTIVE
20-Hydroxyeicosatetraenoic acid has been shown to play an important role in cerebral vascular function. We hypothesized that polymorphisms in genes encoding 20-Hydroxyeicosatetraenoic acid synthesizing enzymes might confer susceptibility to stroke.


RESULTS
To test the hypothesis, haplotype tagging single nucleotide polymorphisms and potential functional polymorphisms of CYP4A11 and CYP4F2 genes were genotyped in 558 ischemic stroke patients, 221 hemorrhagic stroke patients and 557 controls. The association analyses were performed at both single nucleotide polymorphism and haplotype levels. We further verified our findings in an independent cohort of 551 ischemic stroke cases and 48 hemorrhagic stroke cases and 694 unaffected controls. We identified CYP4A11 C-296T and CYP4F2 V433M were associated with significantly increased risk of ischemic stroke (CT+TT vs. CC, adjusted odds ratio: 1.50, 95% confidence interval: 1.17-1.93, Pcombined=0.001, Pcorr=0.008; V/M+M/M vs. V/V, odds ratio: 1.38, 95% confidence interval: 1.15-1.65, Pcombined=5.6x10, Pcorr=0.005, respectively). Interestingly, the effects of CYP4F2 V433M on ischemic stroke in our study was only evident in male individuals.


CONCLUSIONS
Our results suggest that genetic variation in CYP4A11 and CYP4F2 alters susceptibility to stroke in the Han Chinese population.
The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Hu
H
Ding
Guanglin
G
Cui
Lan
L
Zhang
Yujun
Y
Xu
Xunna
X
Bao
Yuanchao
Y
Tu
Bin
B
Wu
Qi
Q
Wang
Rutai
R
Hui
Wei
W
Wang
Ryan T
RT
Dackor
Grace E
GE
Kissling
Darryl C
DC
Zeldin
Dao Wen
DW
Wang
D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors; D020521:Stroke / Q000235:genetics*
D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A