Investigation for the physiological and pathological significance of the interaction between COMT deficiency and homocysteine

与生活方式相关的疾病，如糖尿病、代谢综合征和癌症，都是由遗传因素、生活方式和环境因素相互作用而引起的。考虑到最近此类生活方式相关疾病的流行，表明大多数人确实具有相同的遗传背景，因此这种背景可能是在人类进化过程中获得的。这项资助的申请者建立了第一个遗传性先兆子痫小鼠模型，并揭示了小鼠儿茶酚-O-甲基转移酶(COMT)缺陷是子痫前期发病机制的一个可能解释。与生活方式有关的先兆子痫和代谢缺陷相关疾病都有共同的症状，如葡萄糖耐量不足、高血压和异常肥胖。在我们目前用小鼠模型进行的研究中，我们证实了COMT是脆弱的，在暴露于高脂饮食和怀孕等环境因素时容易受到抑制。

Life style related diseases such as diabetes, metabolic syndrome, and cancer, would be caused by the interaction between genetic factor, life style, and environmental factors. When considering the recent epidemic of such life style related diseases, suggesting that most of people are indeed sharing genetic background and therefore such background is probably acquired for the evolutional process of homo sapience. Applicant of this grant established first genetic mouse model of preeclampsia and revealed catechol metabolism defects in catechol-o-methyltransferase (COMT) deficiency in mice was one possible explanation of preeclampsia pathogenesis. Preeclampsia and metabolic defects in life style related diseases share symptoms, such as glucose intolerance, hypertension, and abnormal adiposity. In our current study using mouse models, we confirmed COMT is fragile and easy to be suppressed in the exposure of environmental factors, such as high fat diet fed and pregnancy.