Association of genetic polymorphisms of endothelin-converting enzyme-1 gene with hypertension in a Japanese population and rare missense mutation in preproendothelin-1 in Japanese hypertensives

Mariko Banno, Hironori Hanada, Kei Kamide, Yoshihiro Kokubo, Akiko Kada, Jin Yang, Chihiro Tanaka, Shin Takiuchi, Takeshi Horio, Tetsutaro Matayoshi, Hisayo Yasuda, Junko Nagura, Hitonobu Tomoike, Yuhei Kawano, Toshiyuki Miyata

研究成果: ジャーナルへの寄稿学術論文査読

21 被引用数 (Scopus)

抄録

Endothelin-1 (EDN1), a 21-amino acid peptide, is a potent vasoconstrictor with various pharmacological responses. EDN1 is synthesized from a 212-amino acid precursor protein, preproEDN1, through multiple proteolytic steps. Endothelin-converting enzyme (ECE) cleaves a Trp73-Val74 peptide bond in big-EDN1 to give rise to mature EDN1. In this study, we examined the possible association of genetic variations in ECE1 with hypertension in a general Japanese population and searched for missense mutations in and around the EDN1 polypeptide. We genotyped 5 single nucleotide polymorphisms (SNPs) in the ECE1 gene in 1,873 individuals from a general Japanese population and identified one SNP associated with hypertension in women (rs212528: TT vs. TC+CC: odds ratio=1.40; 95% confidence intervals: 1.04-1.89; p=0.026), after adjusting for confounding factors. The systolic blood pressure in women with the CC genotype was 6.44 mmHg higher than that in those with the TT genotype (p=0.007), after adjusting for the same factors. Next, to identify the missense mutations that may influence the biological activity of EDN1, we sequenced the genomic region that encodes EDN1 in 942 Japanese hypertensive patients. We identified a novel missense mutation, G36R, in one hypertensive patient, but no mutations were observed in EDN1. A gene polymorphism in EDN1, Lys198Asn, has been reported, to be associated with hypertension in obese subjects. Taken together, these findings reveal that the EDN-ECE pathway is an important system involved in essential hypertension in Japanese.

本文言語英語
ページ(範囲)513-520
ページ数8
ジャーナルHypertension Research
30
6
DOI
出版ステータス出版済み - 06-2007
外部発表はい

All Science Journal Classification (ASJC) codes

  • 内科学
  • 生理学
  • 循環器および心血管医学

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「Association of genetic polymorphisms of endothelin-converting enzyme-1 gene with hypertension in a Japanese population and rare missense mutation in preproendothelin-1 in Japanese hypertensives」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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