Abe Michiko, Wu Zhihong, Yamamoto Miyuki, Jin Jing Ji, Tabara Yasuharu, Mogi Masaki, Kohara Katsuhiko, Miki Tetsuro, Nakura Jun
Department of Geriatric Medicine, School of Medicine, Ehime University, Shitsukawa, Toon 791-0295, Japan.
Hypertens Res. 2005 Mar;28(3):215-21. doi: 10.1291/hypres.28.215.
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.
多巴胺-β-羟化酶（DBH）催化多巴胺转化为去甲肾上腺素，并从交感神经元释放到循环系统中。包括原发性高血压患者血浆DBH活性升高这一发现在内的多项证据表明，DBH在高血压中起重要作用。最近，已证明DBH基因5'侧翼区域的一种新型多态性（-1021C/T）可解释血浆DBH活性35%-52%的变异。因此，我们在一大群日本人群中研究了DBH -1021C/T多态性与高血压之间可能存在的关联。此外，由于高血压的发生至少部分被认为是基因-环境相互作用的结果，我们还研究了DBH -1021C/T多态性与环境因素之间可能存在的相互作用。结果，我们发现DBH -1021C/T多态性与空腹血糖（FPG）在与高血压的关联中存在显著相互作用。CC纯合子与T等位基因携带者相比，随着FPG升高，患高血压的概率上升更为陡峭。我们还发现了一个边缘显著的趋势，提示DBH -1021C/T多态性与FPG在与血压的关联中存在相互作用。与这种相互作用的存在一致，我们发现包含DBH -1021C/T多态性的19 bp序列包含两个由5个碱基对隔开的回文非规范E盒，并且与L型丙酮酸激酶基因的葡萄糖反应元件非常相似。这些发现可能有助于对葡萄糖代谢、交感神经系统和高血压之间的关系进行进一步的分子和生物学研究。
