Endothelin-1 gene variant associates with blood pressure in obese Japanese subjects: The Ohasama study

Takashi Asai, Takayoshi Ohkubo, Tomohiro Katsuya, Jitsuo Higaki, Yuxiao Fu, Masayuki Fukuda, Atsushi Hozawa, Mitsunobu Matsubara, Hirofumi Kitaoka, Ichiro Tsuji, Tsutomu Araki, Hiroshi Satoh, Shigeru Hisamichi, Yutaka Imai, Toshio Ogihara

Research output: Contribution to journalArticlepeer-review

111 Citations (Scopus)


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 Lys 198Asn polymorphism of ET-1 is involved in determination of BP levels in obese subjects.

Original languageEnglish
Pages (from-to)1321-1324
Number of pages4
Issue number6
Publication statusPublished - 2001


  • Genetics
  • Hypertension, essential
  • Insulin resistance
  • Polymerase chain reaction
  • Polymorphism
  • Receptors, endothelin


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