Association of endothelin-1 gene variant with hypertension.
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.
Jin
Jing Ji
JJ
Department of Geriatric Medicine, School of Medicine, Ehime University, Onsen-gun, Ehime, Japan.
Nakura
Jun
J
Wu
Zhihong
Z
Yamamoto
Miyuki
M
Abe
Michiko
M
Tabara
Yasuharu
Y
Yamamoto
Yoshikuni
Y
Igase
Michiya
M
Kohara
Katsuhiko
K
Miki
Tetsuro
T
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
D019332:Endothelin-1