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
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Kynureninase is a novel candidate gene for hypertension in spontaneously hypertensive rats.
掲載誌名	正式名：Hypertension research : official journal of the Japanese Society of Hypertension 略　 称：Hypertens Res ISSNコード：09169636/09169636
掲載区分	国外
巻・号・頁	25(1),pp.135-140
著者・共著者	Mizutani Ken-ichi, Sugimoto Ken, Okuda Tomohiko, Katsuya Tomohiro, Miyata Toshiyuki, Tanabe Tadashi, Higaki Jitsuo, Ogihara Toshio, Yamori Yukio, Tsujita Yasuyuki, Tago Naomi, Iwai Naoharu
発行年月	2002/01
概要	The rostral ventrolateral medulla (RVLM) plays a critical role in the tonic and reflexive regulation of arterial blood pressure. Recent studies have demonstrated that injection of kynurenic acid (KYN) into the RVLM of spontaneously hypertensive rats (SHR) decreases arterial blood pressure. We hypothesized that a relative increase in the excitatory amino acid-mediated drive of RVLM vasomotor neurons in SHR may be due to derangement of one of the enzymes that affect the KYN level in the brain. We selected kynureninase, kynureninase hydroxylase, kynurenine aminotransferase type I, and kynurenine aminotransferase type II as candidates that may affect the KYN level in the brainstem. We conducted association studies between polymorphisms of these genes and blood pressure in an F2 population derived from SHR and Wistar-Kyoto rats (WKY). The cosegregation analysis indicated that only the kynureninase gene (KYNU) polymorphism influenced systolic blood pressure (SBP) and residuals of systolic blood pressure after adjusting for heart rate and body weight (RSBP). KYNU was found to be located on rat chromosome 3, and quantitative trait loci analysis at this locus indicated that the logarithms of the odds scores for KYNU in terms of SBP and RSBP were 2.0 and 3.3, respectively. This association with blood pressure decreased in proportion to the distance from KYNU. The expression level of KYNU mRNA in the brainstem was about 3.1 and 2.9 times higher in 10-week-old and 16-week-old SHR than in age-matched WKY, respectively. The increased expression of KYNU in SHR is thought to decrease the KYN level. KYNU seems to be one of the genes that contributes to hypertension in SHR.
DOI	10.1291/hypres.25.135
PMID	11924719