Yamamoto Miyuki, Jin Jing Ji, Wu Zhihong, Abe Michiko, Tabara Yasuharu, Nagai Tokihisa, Yamasaki Eiji, Igase Michiya, Kohara Katsuhiko, Miki Tetsuro, Nakura Jun
Department of Geriatric Medicine, School of Medicine, Ehime University, Toon, Japan.
Hypertens Res. 2006 Apr;29(4):227-32. doi: 10.1291/hypres.29.227.
Serotonin has been implicated in the pathogenesis of hypertension because of its ability to induce vasoconstriction via stimulation of serotonin 2 (5-HT2) receptors. Recently, an association between the T102C functional polymorphism of the serotonin 2A (5-HT2A) receptor gene and hypertension in the UK has been reported. Another association study, however, failed to replicate this association in a Chinese population. We therefore investigated the possible association between the 5-HT2A T102C polymorphism and hypertension in two large Japanese populations (n = 2,968 total). We also investigated the possible interaction between the 5-HT2A T102C polymorphism and the G/T (Lys198Asn) polymorphism of the endothelin-1 (ET-1) gene, based on robust biological evidence for the existence of an interaction between the serotonin and endothelin systems. The results showed that there was no significant difference in the frequencies of the alleles and genotypes between the hypertensive and normotensive subjects. However, a significant interaction between the 5-HT2A T102C and ET-1 G/T polymorphisms in their association with hypertension (p = 0.0040) and with diastolic blood pressure (p = 0.0013) was revealed. A marginally significant interaction in the association with systolic blood pressure was also shown (p = 0.045). The associations of the 5-HT2A T102C polymorphism with hypertension and diastolic blood pressure in ET-1 T allele carriers were significant (p = 0.0056 and 0.021, respectively). The association of the 5-HT2A T102C polymorphism with systolic blood pressure in ET-1 T allele carriers was marginally significant (p = 0.054). Thus, the present study suggests that the 5-HT2A T102C and ET-1 G/T polymorphisms are interactively associated with hypertension.
血清素因能通过刺激血清素2（5-HT2）受体诱导血管收缩而被认为与高血压的发病机制有关。最近，有报道称在英国血清素2A（5-HT2A）受体基因的T102C功能多态性与高血压之间存在关联。然而，另一项关联研究未能在中国人群中重现这种关联。因此，我们在两个大型日本人群（共2968人）中研究了5-HT2A T102C多态性与高血压之间可能存在的关联。基于血清素和内皮素系统之间存在相互作用的有力生物学证据，我们还研究了5-HT2A T102C多态性与内皮素-1（ET-1）基因的G/T（Lys198Asn）多态性之间可能存在的相互作用。结果显示，高血压患者和血压正常者之间的等位基因和基因型频率没有显著差异。然而，研究发现5-HT2A T102C和ET-1 G/T多态性在与高血压（p = 0.0040）和舒张压（p = 0.0013）的关联中存在显著的相互作用。在与收缩压的关联中也显示出边缘显著的相互作用（p = 0.045）。在ET-1 T等位基因携带者中，5-HT2A T102C多态性与高血压和舒张压的关联具有显著性（分别为p = 0.0056和0.021）。在ET-1 T等位基因携带者中，5-HT2A T102C多态性与收缩压的关联具有边缘显著性（p = 0.054）。因此，本研究表明5-HT2A T102C和ET-1 G/T多态性与高血压存在交互关联。
