Ken Sugimoto
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of General Geriatric Medicine,
   Position   Professor
Article types 原著
Language English
Peer review Peer reviewed
Title A polymorphism regulates CYP4A11 transcriptional activity and is associated with hypertension in a Japanese population.
Journal Formal name：Hypertension (Dallas, Tex. : 1979)
Abbreviation：Hypertension
ISSN code：15244563/0194911X
Domestic / ForeginForegin
Volume, Issue, Page 52(6),pp.1142-1148
Author and coauthor Sugimoto Ken, Akasaka Hiroshi, Katsuya Tomohiro, Node Koichi, Fujisawa Tomomi, Shimaoka Izumi, Yasuda Osamu, Ohishi Mitsuru, Ogihara Toshio, Shimamoto Kazuaki, Rakugi Hiromi
Publication date 2008/12
Summary CYP4A11 oxidizes arachidonic acid to 20-hydroxyeicosatetraenoic acid, a metabolite with renovascular and tubular function in humans. A previous study demonstrated a significant association between the CYP4A11 gene polymorphism and hypertension; however, the precise mechanism of the association has not been clarified. To assess the involvement of CYP4A11 in the pathogenesis of hypertension, we sought to identify a functional polymorphism of CYP4A11 and examined its impact on predisposition to hypertension in the Tanno-Sobetsu Study. The -845A/G polymorphism was identified in the promoter region of CYP4A11 by direct sequencing. Luciferase expression driven by the promoter of CYP4A11 containing the wild-type -845GG genotype was 30% lower than expression with the variant -845AA genotype. Gel mobility shift assays with nuclear protein extracts showed specific binding to probes containing the variant -845GG. To assess the effect of CYP4A11 polymorphisms on hypertension, we also carried out a case-control study using 4 single nucleotide polymorphisms (-845A/G, -366C/T, 7119C/T, and 8590T/C) in the Tanno-Sobetsu Study. The odds ratio for hypertension in participants with the AG+GG genotype of -845A/G was 1.42 (P=0.008), and the odds ratio for hypertension of the TT genotype of 7119C/T was 1.37 (P=0.037) after adjusting for confounding factors. The haplotype-based case-control analysis using 4 single nucleotide polymorphisms revealed a significant haplotype (G-C-T-T) that was significantly associated with hypertension, with an odds ratio of 1.44 (P=0.006) after adjusting for confounding factors. We have identified a functional variant (-845A/G) of CYP4A11 that is significantly associated with hypertension and that appears to be a novel candidate for a predisposing factor for hypertension.
DOI 10.1161/HYPERTENSIONAHA.108.114082
PMID 18936345