A Haplotype of the CYP4F2 Gene is Associated With Cerebral Infarction in Japanese Men

被引:34
作者
Fu, Zhenyan [1 ,2 ]
Nakayama, Tomohiro [1 ,3 ]
Sato, Naoyuki [1 ]
Izumi, Yoichi [3 ]
Kasamaki, Yuji [4 ]
Shindo, Atsushi [4 ]
Ohta, Masakatsu [4 ]
Soma, Masayoshi [3 ,5 ]
Aoi, Noriko [1 ,3 ]
Sato, Mikano [1 ,3 ]
Matsumoto, Koichi [3 ]
Ozawa, Yukio [4 ]
Ma, Yitong
机构
[1] Nihon Univ, Sch Med, Dept Adv Med Sci, Div Mol Diagnost, Tokyo, Japan
[2] Xinjiang Med Univ, Affiliated Hosp 1, Dept Cardiovasc Med, Urumqi, Peoples R China
[3] Nihon Univ, Sch Med, Dept Med, Div Nephrol & Endocrinol, Tokyo, Japan
[4] Nihon Univ, Sch Med, Dept Med, Div Cardiovasc Med, Tokyo, Japan
[5] Nihon Univ, Sch Med, Dept Med, Div Gen Med, Tokyo, Japan
关键词
D O I
10.1038/ajh.2008.276
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
BACKGROUND CYP4F2, a member of the cytochrome P450 family, acts mainly as an enzyme and is involved not only in the metabolism of leukotriene 134, but also in that of arachidonic acid. It converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite involved in the regulation of the vascular tone in the brain. The aim of this study was to assess the association between the human CYP4F2 gene and cerebral infarction (CI), using a haplotype-based case-control study with separate analyses of data from the gender groups. METHODS A total of 175 Cl patients and 246 control subjects were genotyped for five single-nucleotide polymorphisms (SNPs) of the human CYP4F2 gene (rs3093105, rs3093135, rs1558139, rs2108622, rs3093200). For data analysis, three separate groups were assessed: all subjects, men, and women. RESULTS In the male subjects, the G allele frequency for rs2108622 was significantly higher in Cl patients as compared to control subjects (P = 0.025). The overall distribution of the haplotypes in the men was significantly different between the Cl patients and the control subjects (P= 0.027). Additionally, the frequency of the T-C-G haplotype for men was significantly higher in the Cl patients than in the control subjects (P = 0.008). Multiple logistic regression analysis also revealed the significance of the T-C-G haplotype in men, even after adjustment for confounding factors. CONCLUSIONS The results of this study indicate that, in Japanese men, Cl is associated with the G allele of rs2108622 and, in addition, that the T C-G haplotype appears to be a useful genetic marker for Cl. Am J Hypertens 2008;21:1216-1223 (C) 2008 American Journal of Hypertension, Ltd.
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收藏
页码:1216 / 1223
页数:8
相关论文
共 35 条
[11]   Testosterone treatment increases thromboxane function in rat cerebral arteries [J].
Gonzales, RJ ;
Ghaffari, AA ;
Duckles, SP ;
Krause, DN .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2005, 289 (02) :H578-H585
[12]   FORMATION AND ACTION OF A P-450 4A METABOLITE OF ARACHIDONIC-ACID IN CAT CEREBRAL MICROVESSELS [J].
HARDER, DR ;
GEBREMEDHIN, D ;
NARAYANAN, J ;
JEFCOAT, C ;
FALCK, JR ;
CAMPBELL, WB ;
ROMAN, R .
AMERICAN JOURNAL OF PHYSIOLOGY, 1994, 266 (05) :H2098-H2107
[13]   Sensitivity to cerebral ischaemic insult in a rat model of stroke is determined by a single genetic locus [J].
Jeffs, B ;
Clark, JS ;
Anderson, NH ;
Gratton, J ;
Brosnan, MJ ;
Gauguier, D ;
Reid, JL ;
Macrae, IM ;
Dominiczak, AF .
NATURE GENETICS, 1997, 16 (04) :364-367
[14]  
Lanca V, 2004, Rev Port Cardiol, V23, P343
[15]   20-hydroxyeicosatetraenoic acid-induced vasoconstriction and inhibition of potassium current in cerebral vascular smooth muscle is dependent on activation of protein kinase C [J].
Lange, A ;
Gebremedhin, D ;
Narayanan, J ;
Harder, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (43) :27345-27352
[16]   Formation of 20-hydroxyeicosatetraenoic acid, a vasoactive and natriuretic eicosanoid, in human kidney - Role of CYP4F2 and CYP4A11 [J].
Lasker, JM ;
Chen, WB ;
Wolf, I ;
Bloswick, BP ;
Wilson, PD ;
Powell, PK .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (06) :4118-4126
[17]  
Ma Ai-jun, 2006, Zhonghua Yixue Yichuanxue Zazhi, V23, P202
[18]   Down-regulation of astroglial CYP2C, glucocorticoid receptor and constitutive androstane receptor genes in response to cocaine in human U373 MG astrocytoma cells [J].
Malaplate-Armand, C ;
Ferrari, L ;
Masson, C ;
Visvikis-Siest, S ;
Lambert, H ;
Batt, AM .
TOXICOLOGY LETTERS, 2005, 159 (03) :203-211
[19]  
McCullough LD, 2003, J NEUROSCI, V23, P8701
[20]   Beneficial effects of a new 20-hydroxyeicosatetraenoic acid synthesis inhibitor, TS-011 [N-(3-chloro-4-morpholin-4-yl) phenyl-N′-hydroxyimido formamide], on hemorrhagic and ischemic stroke. [J].
Miyata, N ;
Seki, T ;
Tanaka, Y ;
Omura, T ;
Taniguchi, K ;
Doi, M ;
Bandou, K ;
Kametani, S ;
Sato, M ;
Okuyama, S ;
Cambj-Sapunar, L ;
Harder, DR ;
Roman, RJ .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 314 (01) :77-85