スギモト ケン
Ken Sugimoto
杉本 研 所属 川崎医科大学 医学部 臨床医学 総合老年医学 職種 教授 |
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論文種別 | 原著 |
言語種別 | 英語 |
査読の有無 | 査読あり |
表題 | A polymorphism regulates CYP4A11 transcriptional activity and is associated with hypertension in a Japanese population. |
掲載誌名 | 正式名:Hypertension (Dallas, Tex. : 1979) 略 称:Hypertension ISSNコード:15244563/0194911X |
掲載区分 | 国外 |
巻・号・頁 | 52(6),pp.1142-1148 |
著者・共著者 | Sugimoto Ken, Akasaka Hiroshi, Katsuya Tomohiro, Node Koichi, Fujisawa Tomomi, Shimaoka Izumi, Yasuda Osamu, Ohishi Mitsuru, Ogihara Toshio, Shimamoto Kazuaki, Rakugi Hiromi |
発行年月 | 2008/12 |
概要 | 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 |