Endothelin-1 gene variant associates with blood pressure in obese Japanese subjects: the Ohasama Study.
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 (> or =25 kg/m(2)) 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.
Asai
T
T
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Ohkubo
T
T
Katsuya
T
T
Higaki
J
J
Fu
Y
Y
Fukuda
M
M
Hozawa
A
A
Matsubara
M
M
Kitaoka
H
H
Tsuji
I
I
Araki
T
T
Satoh
H
H
Hisamichi
S
S
Imai
Y
Y
Ogihara
T
T
D044466:Asian People / Q000235:genetics*; D015897:Comorbidity; D015986:Confounding Factors, Epidemiologic; D003710:Demography; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology* / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology*; D011110:Polymorphism, Genetic; D044465:White People / Q000235:genetics
D019332:Endothelin-1