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.
引用
收藏
页码:1216 / 1223
页数:8
相关论文
共 35 条
[1]   Neuroprotection and P4502C11 upregulation after experimental transient ischemic attack [J].
Alkayed, NJ ;
Goyagi, T ;
Joh, HD ;
Klaus, J ;
Harder, DR ;
Traystman, RJ ;
Hurn, PD .
STROKE, 2002, 33 (06) :1677-1684
[2]   Contribution of 5-hydroxytryptamine1B receptors and 20-hydroxyeiscosatetraenoic acid to fall in cerebral blood flow after subarachnoid hemorrhage [J].
Cambj-Sapunar, L ;
Yu, M ;
Harder, DR ;
Roman, RJ .
STROKE, 2003, 34 (05) :1269-1275
[3]   Microsomal cytochrome P450 and eicosanoid metabolism [J].
Capdevila, JH ;
Harris, RC ;
Falck, JR .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2002, 59 (05) :780-789
[4]   Angiotensin-converting enzyme insertion deletion polymorphism and cerebrovascular disease [J].
Catto, A ;
Carter, AM ;
Barrett, JH ;
Stickland, M ;
Bamford, J ;
Davies, JA ;
Grant, PJ .
STROKE, 1996, 27 (03) :435-440
[5]   PREVALENCE OF APOLIPOPROTEIN-E PHENOTYPES IN ISCHEMIC CEREBROVASCULAR-DISEASE - A CASE-CONTROL STUDY [J].
COUDERC, R ;
MAHIEUX, F ;
BAILLEUL, S ;
FENELON, G ;
MARY, R ;
FERMANIAN, J .
STROKE, 1993, 24 (05) :661-664
[6]   Cytochrome P450 enzymes: Central players in cardiovascular health and disease [J].
Elbekai, Reem H. ;
El-Kadi, Ayman O. S. .
PHARMACOLOGY & THERAPEUTICS, 2006, 112 (02) :564-587
[7]  
FERENCHICK GS, 1990, NEW ENGL J MED, V322, P476
[8]   A haplotype of the CYP4A11 gene associated with essential hypertension in Japanese men [J].
Fu, Zhenyan ;
Nakayama, Tomohiro ;
Sato, Naoyuki ;
Izumi, Yoichi ;
Kasamaki, Yuji ;
Shindo, Atsushi ;
Ohta, Masakatsu ;
Soma, Masayoshi ;
Aoi, Noriko ;
Sato, Mikano ;
Ozawa, Yukio ;
Ma, Yitong .
JOURNAL OF HYPERTENSION, 2008, 26 (03) :453-461
[9]   Cat cerebral arterial smooth muscle cells express cytochrome P450 4A2 enzyme and produce the vasoconstrictor 20-HETE which enhances L-type Ca2+ current [J].
Gebremedhin, D ;
Lange, AR ;
Narayanan, J ;
Aebly, MR ;
Jacobs, ER ;
Harder, DR .
JOURNAL OF PHYSIOLOGY-LONDON, 1998, 507 (03) :771-781
[10]   Production of 20-HETE and its role in autoregulation of cerebral blood flow [J].
Gebremedhin, D ;
Lange, AR ;
Lowry, TF ;
Taheri, MR ;
Birks, EK ;
Hudetz, AG ;
Narayanan, J ;
Falck, JR ;
Okamoto, H ;
Roman, RJ ;
Nithipatikom, K ;
Campbell, WB ;
Harder, DR .
CIRCULATION RESEARCH, 2000, 87 (01) :60-65