Positive Association Between the Lys198 Asn Polymorphism in the Endothelin-1 and Blood Pressure in Obese Japanese Subjects: Ohasama Study
A recent report by Tiret et al. (Hypertension 33, 1999) revealed that a G/T polymorphism with an amino acid substitution (Lys to Asn) at codon 198 in the exon 5 of endothelin 1 gene (ET1) is associated with blood pressure in overweight people using two epidemiological studies, ECTIM and Glasgow Heart Scan Study. They suggested that G/T polymorphism strongly interacted with body mass index (BMI) in the determination of blood pressure levels. To examine the interaction among G/T polymorphism of ET1, BMI and blood pressure, we carried out an association study using a general population. Subjects (n=1,446) were recruited from Ohasama population, which is a cohort in a rural community of northern Japan. The research protocol was approved by the Institutional Review Board of the Tohoku University. DNA was extracted from the buffy coat of the participants using QIAamp DNA Blood Kit (Qiagen Inc.). G/T polymorphism of ET1 was determined by TaqMan PCR method, which is a powerful tool for semiautomatic genotype determination in a large number of samples. The frequency of T198 allele in Japanese (26%) was significantly higher than that in Caucasians (23%). The baseline characteristic (age, BMI, SBP, DBP, antihypertensive treatment) of all subjects was not significantly different according to the genotype of G/T polymorphism. In the obese subjects (≥25kg/m2), however, SBP and DBP were significantly associated with G/T polymorphism. Blood pressure level in the subjects carrying T198 allele was 2.6 mmHg in systolic (p<0.02) and 2.3 mmHg in diastolic (p<0.005) higher than that in those with GG genotype in overweight people. That the same result was obtained from different races suggested that the T198 allele of ET1 is involved in the determination of blood pressure levels in obese subjects.