doi: 10.1161/hy1101.095333
(Hypertension. 2001;38:1321.)
© 2001 American Heart Association, Inc.
Scientific Contributions |
Endothelin-1 Gene Variant Associates With Blood Pressure in Obese Japanese Subjects
The Ohasama Study
From the Department of Geriatric Medicine, Osaka University Graduate School of Medicine (T. Asai, T. Ohkubo, T.K., J.H., Y.F., M.F.), Suita; the Departments of Clinical Pharmacology and Therapeutics (M.M., T. Araki, Y.I.), Public Health (A.H., I.T., S.H., T. Ogihara), and Environmental Health Science (H.S.), Tohoku University Graduate School of Medicine and Pharmaceutical Science, Sendai; and Ohasama Hospital (H.K.), Iwate, Japan.
Correspondence to Jitsuo Higaki, MD, PhD, Associate Professor of Medicine, Department of Geriatric Medicine, Osaka University Medical School, 2-2 No. B6, Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail higaki{at}geriat.med.osaka-u.ac.jp
A recent report based on the results of 2 epidemiological studies, the Etude Cas-Temoin de l’Infarctus Myocarde (ECTIM) and the Glasgow Heart Scan Study, revealed that a G/T polymorphism with an amino acid substitution (Lys
Asn) at codon 198 in exon 5 of the endothelin-1 gene (ET-1) is associated with blood pressure in overweight people. They suggested that G/T polymorphism of ET-1 strongly interacted with body mass index (BMI) in the determination of BP levels. To examine interaction among G/T polymorphism of ET-1, BMI, and BP, we performed an association study in a general Japanese population. Subjects (n=1250) were recruited from Ohasama, a cohort in a rural community of northern Japan. DNA was extracted from buffy coat of participants, and G/T polymorphism of ET-1 was determined by the TaqMan probe polymerase chain reaction method, a powerful tool for semiautomatic genotype determination of a large number of samples. Frequency of T (Asn 198) allele in Japanese (27%) was slightly but significantly higher than in whites (24%). Baseline characteristics (age, BMI, systolic and diastolic BP, and antihypertensive treatment) of all subjects were not significantly different according to the genotype of G/T polymorphism. However, in obese subjects (
25 kg/m2) diastolic BPs were significantly associated with G/T polymorphism of ET-1. After adjustment for confounding factors, significant association remained; for overweight subjects, diastolic BP level in those with T allele (GT + TT) was 1.8 mm Hg (P=0.04) higher than in those with GG genotype. That similar results were obtained from subjects of different races suggests that the Lys198Asn polymorphism of ET-1 is involved in determination of BP levels in obese subjects.
Key Words: genetics • hypertension, essential • insulin resistance • polymerase chain reaction • polymorphism • receptors, endothelin
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