Association of dopamine beta-hydroxylase polymorphism with hypertension through interaction with fasting plasma glucose in Japanese.
Dopamine-beta-hydroxylase (DBH) catalyzes the conversion of dopamine to norepinephrine and is released from sympathetic neurons into the circulation. Several lines of evidence, including the finding of elevated plasma DBH activity in essential hypertension, suggest an important role of DBH in hypertension. Recently, a novel polymorphism (-1021C/T) in the 5' flanking region of the DBH gene has been shown to account for 35-52% of the variation in plasma DBH activity. We therefore investigated the possible association between the DBH -1021C/T polymorphism and hypertension in a large Japanese population. Moreover, because the development of hypertension is considered to be due at least partly to gene-environmental interactions, we also investigated the possible interactions between the DBH -1021C/T polymorphism and environmental factors. Consequently, we found a significant interaction between the DBH -1021C/T polymorphism and fasting plasma glucose (FPG) in the association with hypertension. CC homozygotes showed a steeper increase in probability of hypertension with FPG than T allele carriers. We also found a marginally significant trend suggesting the presence of an interaction between the DBH -1021C/T polymorphism and FPG in the association with blood pressure. Consistent with the presence of the interaction, we found that a 19 bp sequence containing the DBH -1021C/T polymorphism includes two palindromic non-canonical E boxes separated by 5 bps, and closely resembles the glucose response element of the L-type pyruvate kinase gene. These findings could be helpful in conducting further molecular and biological studies on the relationship among glucose metabolism, the sympathetic nervous system, and hypertension.
Abe
Michiko
M
Department of Geriatric Medicine, School of Medicine, Ehime University, Shitsukawa, Toon 791-0295, Japan.
Wu
Zhihong
Z
Yamamoto
Miyuki
M
Jin
Jing Ji
JJ
Tabara
Yasuharu
Y
Mogi
Masaki
M
Kohara
Katsuhiko
K
Miki
Tetsuro
T
Nakura
Jun
J
D000368:Aged; D001786:Blood Glucose; D001794:Blood Pressure / Q000235:genetics; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D005215:Fasting; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
D001786:Blood Glucose; D004299:Dopamine beta-Hydroxylase