A haplotype of the CYP4A11 gene associated with essential hypertension in Japanese men
A haplotype of the CYP4A11 gene associated with essential hypertension in Japanese men
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DOI：
10.1097/hjh.0b013e3282f2f10c
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发表时间：
2008-03
影响因子：
4.9
通讯作者：
Z. Fu;T. Nakayama;N. Sato;Y. Izumi;Y. Kasamaki;Atsushi Shindo;M. Ohta;M. Soma;Noriko Aoi;Mikano Sato;Y. Ozawa;Yi-tong Ma
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文献类型：
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作者：
Z. Fu;T. Nakayama;N. Sato;Y. Izumi;Y. Kasamaki;Atsushi Shindo;M. Ohta;M. Soma;Noriko Aoi;Mikano Sato;Y. Ozawa;Yi-tong Ma
目的CYP 4A 11是细胞色素P450家族的成员之一，主要是将花生四烯酸转化为20-羟基二十碳四烯酸的酶，而20-羟基二十碳四烯酸是人体血压调节的代谢产物。最近有报道称，小鼠cyp 4a 14和cyp 4a 10基因（人CYP 4A 11的同源物）的破坏可引起高血压。基因破坏的雄性小鼠的血压高于基因破坏的雌性小鼠。本研究的目的是评估人类CYP 4A 11基因与原发性高血压之间的关联，采用基于单体型的病例对照研究，包括性别组的单独分析。方法对304例原发性高血压患者和207例正常对照者进行CYP 4A 11基因rs 2269231、rs 1126742、rs 9333025单核苷酸多态性基因分型。对三个独立组的数据进行了评估：总参与者，男性和女性。结果两组受试者rs 1126742基因型分布差异有统计学意义（P = 0.005）。对于所有参与者，男性和女性，rs 1126742的隐性模型（CC与TC + TT）在两组之间存在显著差异（分别为P = 0.007，P = 0.043和P = 0.045）。Logistic回归分析显示，原发性高血压患者TC + TT基因型显著高于对照组（P = 0.022和P = 0.043）。男性原发性高血压患者A-T-G单倍型频率（rs 2269231、rs 1126742、rs 9333025）显著高于对照组（P = 0.043）。结论原发性高血压与CYP 4A 11基因rs 1126742的TC + TT基因型有关。A-T-G单倍型似乎是日本男性原发性高血压的一个有用的遗传标记。
Objective CYP4A11, a member of the cytochrome P450 family, acts mainly as an enzyme that converts arachidonic acid to 20-hydroxyeicosatetraenoic acid, a metabolite involved in blood pressure regulation in humans. Disruption of the murine cyp4a14 and cyp4a10 genes, homologues of human CYP4A11, was reported recently to cause hypertension. The gene-disrupted male mice had higher blood pressure than the gene-disrupted female mice. The present study aimed to assess the association between the human CYP4A11 gene and essential hypertension, using a haplotype-based case–control study including separate analysis of the gender groups. Methods The 304 essential hypertension patients and 207 age-matched control individuals were genotyped for three single-nucleotide polymorphisms of the human CYP4A11 gene (rs2269231, rs1126742, rs9333025). Data were assessed for three separate groups: total participants, men and women. Results For total participants, the genotypic distribution of rs1126742 differed significantly between the two groups (P = 0.005). For total participants, men and women, the recessive model (CC versus TC + TT) of rs1126742 differed significantly between the two groups (P = 0.007, P = 0.043, and P = 0.045, respectively). Logistic regression analysis showed the TC + TT genotype was significantly higher in essential hypertension patients than in control individuals for total participants and men (P = 0.022 and P = 0.043, respectively). The A-T-G haplotype frequency (established by rs2269231, rs1126742, rs9333025) was significantly higher in essential hypertension men than in control men (P = 0.043). Conclusions Essential hypertension is associated with the TC + TT genotype of rs1126742 in the human CYP4A11 gene. The A-T-G haplotype appears a useful genetic marker of essential hypertension in Japanese men.