This Article Full Text Full Text (PDF) All Versions of this Article: 41/1/163    most recent 01.HYP.0000043680.75107.CFv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jin, J. J. Articles by Miki, T. Search for Related Content PubMed PubMed Citation Articles by Jin, J. J. Articles by Miki, T. Related Collections Clinical genetics

(Hypertension. 2003;41:163.)
© 2003 American Heart Association, Inc.

Scientific Contributions

Association of Endothelin-1 Gene Variant With Hypertension

Jing Ji Jin; Jun Nakura; Zhihong Wu; Miyuki Yamamoto; Michiko Abe; Yasuharu Tabara; Yoshikuni Yamamoto; Michiya Igase; Katsuhiko Kohara; Tetsuro Miki

From the Department of Geriatric Medicine, School of Medicine, Ehime University, Ehime, Japan.

Correspondence to Dr Jun Nakura, Department of Geriatric Medicine, School of Medicine, Ehime University, Shigenobu-cho, Onsen-gun, Ehime 791-0295, Japan. E-mail nakura{at}m.ehime-u.ac.jp

Endothelin-1 (ET-1) is a powerful vasoconstrictor peptide produced by endothelial and smooth muscle cells. Many lines of biological evidence suggest that the ET-1 gene is a candidate gene for hypertension. Moreover, recent association studies suggested that a G/T polymorphism with an amino acid substitution (Lys/Asn) at codon 198 in exon 5 of the ET-1 gene interacts with body mass index (BMI) in association with blood pressure. They suggested that T carriers are more sensitive to weight gain than GG homozygotes in association with blood pressure. However, association studies are often irreproducible, and the first study often suggests a stronger genetic effect than is found by subsequent studies. We therefore assessed the interaction in 2 large Japanese populations. The present study showed a nonsignificant but similar trend to the results of previous reports. Moreover, in line with previous reports, this study revealed a significant interaction between the ET-1 K198N (G/T) polymorphism and BMI in association with hypertension in our populations (P=0.027). The interaction was significant, even after adjustment for gender and age (P=0.045) and for all confounding factors (P=0.044). T carriers were more sensitive to weight gain than GG homozygotes in association with hypertension. Considering the combined impact of obesity and hypertension on the development of cardiovascular and cerebrovascular disorders, T allele carriers might represent elective targets for therapy to lower their body weight.

Key Words: endothelin • hypertension, essential • genetics • polymorphism • body mass index

This article has been cited by other articles:

				T. Rankinen, T. Church, T. Rice, N. Markward, A. S. Leon, D. C. Rao, J. S. Skinner, S. N. Blair, and C. Bouchard Effect of Endothelin 1 Genotype on Blood Pressure Is Dependent on Physical Activity or Fitness Levels Hypertension, December 1, 2007; 50(6): 1120 - 1125. [Abstract] [Full Text] [PDF]

				D. K. Arnett, A. E. Baird, R. A. Barkley, C. T. Basson, E. Boerwinkle, S. K. Ganesh, D. M. Herrington, Y. Hong, C. Jaquish, D. A. McDermott, et al. Relevance of Genetics and Genomics for Prevention and Treatment of Cardiovascular Disease: A Scientific Statement From the American Heart Association Council on Epidemiology and Prevention, the Stroke Council, and the Functional Genomics and Translational Biology Interdisciplinary Working Group Circulation, June 5, 2007; 115(22): 2878 - 2901. [Abstract] [Full Text] [PDF]

				E. Thomson, P. Kumarathasan, P. Goegan, R. A. Aubin, and R. Vincent Differential Regulation of the Lung Endothelin System by Urban Particulate Matter and Ozone Toxicol. Sci., November 1, 2005; 88(1): 103 - 113. [Abstract] [Full Text] [PDF]

				Y. Dong, X. Wang, H. Zhu, F. A. Treiber, and H. Snieder Endothelin-1 Gene and Progression of Blood Pressure and Left Ventricular Mass: Longitudinal Findings in Youth Hypertension, December 1, 2004; 44(6): 884 - 890. [Abstract] [Full Text] [PDF]

				K. Diefenbach, F. A. Nahad, C. Meisel, I. Fietze, I. Cascorbi, K. Stangl, O. Landt, R. Kerb, U. Brinkmann, and I. Roots Identification of Twelve Polymorphisms in the Endothelin-1 Gene by Use of Fluorescently Labeled Oligonucleotides and PCR with Restriction Fragment Polymorphism Analysis Clin. Chem., February 1, 2004; 50(2): 448 - 451. [Full Text] [PDF]

				C. Cardillo, U. Campia, M. Iantorno, and J. A. Panza Enhanced Vascular Activity of Endogenous Endothelin-1 in Obese Hypertensive Patients Hypertension, January 1, 2004; 43(1): 36 - 40. [Abstract] [Full Text] [PDF]