title: A haplotype of the CYP4A11 gene associated with essential hypertension in Japanese men.
abstract: 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.
authors.affiliation: Division of Molecular Diagnostics, Department of Advanced Medical Science, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Zhenyan
authors.initials: Z
authors.lastname: Fu
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nakayama
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Sato
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Izumi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kasamaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shindo
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Ohta
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.forename: Noriko
authors.initials: N
authors.lastname: Aoi
authors.forename: Mikano
authors.initials: M
authors.lastname: Sato
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Yitong
authors.initials: Y
authors.lastname: Ma
mesh_terms: D000368:Aged; D000818:Animals; D016022:Case-Control Studies; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D006239:Haplotypes; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007564:Japan; D008297:Male; D051379:Mice; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers; D003577:Cytochrome P-450 Enzyme System; C465478:CYP4A11 protein, human; D042926:Cytochrome P-450 CYP4A