Published Online
on November 25, 2002

A more recent version of this article appeared on January 1, 2003

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Submitted on June 27, 2002
Revised on September 11, 2002

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; and Tetsuro Miki

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

^* To whom correspondence should be addressed. E-mail: nakura{at}m.ehime-u.ac.jp.

Abstract—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

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