title: Association of endothelin-1 gene variant with hypertension.
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.
authors.affiliation: Department of Geriatric Medicine, School of Medicine, Ehime University, Onsen-gun, Ehime, Japan.
authors.forename: Jing Ji
authors.initials: JJ
authors.lastname: Jin
authors.forename: Jun
authors.initials: J
authors.lastname: Nakura
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wu
authors.forename: Miyuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Michiko
authors.initials: M
authors.lastname: Abe
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Tabara
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Michiya
authors.initials: M
authors.lastname: Igase
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Kohara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Miki
mesh_terms: D001794:Blood Pressure; D015992:Body Mass Index; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D019332:Endothelin-1