Fu Zhenyan, Nakayama Tomohiro, Sato Naoyuki, Izumi Yoichi, Kasamaki Yuji, Shindo Atsushi, Ohta Masakatsu, Soma Masayoshi, Aoi Noriko, Sato Mikano, Ozawa Yukio, Ma Yitong
Division of Molecular Diagnostics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan.
J Hypertens. 2008 Mar;26(3):453-61. doi: 10.1097/HJH.0b013e3282f2f10c.
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.
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.
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).
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.
细胞色素P450家族成员CYP4A11主要作为一种将花生四烯酸转化为20-羟基二十碳四烯酸的酶，该代谢产物参与人体血压调节。最近有报道称，破坏小鼠cyp4a14和cyp4a10基因（人类CYP4A11的同源基因）会导致高血压。基因敲除的雄性小鼠血压高于基因敲除的雌性小鼠。本研究旨在通过基于单倍型的病例对照研究（包括对性别组的单独分析）来评估人类CYP4A11基因与原发性高血压之间的关联。
对304例原发性高血压患者和207例年龄匹配的对照个体进行人类CYP4A11基因的三个单核苷酸多态性（rs2269231、rs1126742、rs9333025）基因分型。对三个独立组的数据进行评估：总参与者、男性和女性。
对于总参与者，两组之间rs1126742的基因型分布存在显著差异（P = 0.005）。对于总参与者、男性和女性，rs1126742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）。逻辑回归分析显示，对于总参与者和男性，原发性高血压患者的TC + TT基因型显著高于对照个体（分别为P = 0.022和P = 0.043）。原发性高血压男性中由rs2269231、rs1126742、rs9333025确定的A-T-G单倍型频率显著高于对照男性（P = 0.043）。
原发性高血压与人类CYP4A11基因中rs1126742的TC + TT基因型相关。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。
