Haplotype-based case study of human CYP4A11 gene and cerebral infarction in Japanese subject.
OBJECTIVE
CYP4A11 is an enzyme that converts arachidonic acid to 20-hydroxyeicosatetraenoic acid, which is involved in regulation of vascular tone in the brain. Recent evidence indicates that the polymorphism of the CYP genes is associated with cerebral infarction (CI). The aim of the present study was to assess the association between the human CYP4A11 gene and CI using a haplotype-based case-control study divided by gender.


METHODS
Three SNPs of the human CYP4A11 gene (rs2269231, rs1126742, and rs9333025) were selected and genotyped for 174 CI patients and 293 controls. The data were assessed for three separate groups: total subjects, men and women.


RESULTS
In men, the genotype distribution of rs9333025 significantly differed between the CI patients and control subjects (P = 0.047). The distribution of the dominant model of rs9333025 (GG vs. GA + AA) significantly differed between both the total and the men groups (P = 0.033, P = 0.028, respectively). Logistic regression analysis adjusted for the history of hypertension and diabetes mellitus also showed that the GG genotype was significantly more frequent in the CI patients than in the controls, both for the total and men groups (P < 0.001, P = 0.008, respectively). The overall distribution of the haplotypes constructed with the 3 SNPs showed significant differences between the CI and the control in total group (P = 0.049). The T-C-G haplotype was significantly more frequent in control subjects than in the CI patients in the total group (P = 0.020).


CONCLUSIONS
The GG genotype of rs9333025 could be a genetic marker for CI in Japanese men. In addition, the T-C-G haplotype might also be a protective marker for CI in Japanese.
Fu
Zhenyan
Z
Division of Molecular Diagnostics, Department of Advanced Medical Science, Nihon University School of Medicine, 30-1 Ooyaguchi-kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan.
Nakayama
Tomohiro
T
Sato
Naoyuki
N
Izumi
Yoichi
Y
Kasamaki
Yuji
Y
Shindo
Atsushi
A
Ohta
Masakatsu
M
Soma
Masayoshi
M
Aoi
Noriko
N
Sato
Mikano
M
Matsumoto
Koichi
K
Ozawa
Yukio
Y
Ma
Yitong
Y
D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000235:genetics* / Q000473:pathology; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000235:genetics; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
D005819:Genetic Markers; D006893:Hydroxyeicosatetraenoic Acids; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D003577:Cytochrome P-450 Enzyme System; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A