A single nucleotide polymorphism in the carboxylesterase gene is associated with the responsiveness to imidapril medication and the promoter activity
A single nucleotide polymorphism in the carboxylesterase gene is associated with the responsiveness to imidapril medication and the promoter activity
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DOI：
10.1291/hypres.28.719
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发表时间：
2005-09-01
影响因子：
5.4
通讯作者：
Katagiri, T
中科院分区：
文献类型：
--
作者：
Geshi, E;Kimura, T;Katagiri, T
吡咪普利是一种血管紧张素转换酶抑制剂，广泛用于治疗高血压，尽管个体的反应不同。我们研究了在肝脏中激活咪唑普利的羧酸酯酶1 （CES1）基因-816位的单核苷酸多态性是否与咪唑普利药物的反应性有关。105例收缩压/舒张压（SBP/DBP）为140190 mmHg或更高的日本高血压患者给予5-10 mg/天的米吡普利治疗。在基线时，携带和不携带-816C等位基因的患者的血压水平没有差异（AA组与AC+CC组）。治疗8周后，我们根据血压的下降情况对反应者和无反应者进行分类，发现AC+CC组的反应率明显高于AA组（p=0.0331）。此外，AC+CC组的收缩压降低明显大于AA组（24.7 +/- 11.8 vs. 17.6 +/- 16.8 mmHg, p=0.0184）。此外，体外报告基因实验显示-816C结构具有显著更高的启动子活性(p
Imidapril is an angiotensin-converting enzyme inhibitor that is widely used in treating hypertension, although the responses vary among individuals. We investigated whether a single nucleotide polymorphism at position -816 of the carboxylesterase 1 (CES1) gene, which activates imidapril in the liver, is involved in the responsiveness to imidapril medication. A total of 105 Japanese hypertensives with systolic/diastolic blood pressures (SBP/DBP) of 140190 mmHg or higher were prescribed 5-10 mg/day of imidapril. At baseline, blood pressure levels were not different between patients with and those without the -816C allele (AA vs. AC+CC groups). After 8 weeks of treatment, we classified the responders and non-responders based on the decline in their blood pressures, and found that the responder rate was significantly higher in the AC+CC group than in the AA group (p=0.0331). Also, the reduction in SBP was significantly greater in the AC+CC group than in the AA group (24.7 +/- 11.8 vs. 17.6 +/- 16.8 mmHg, p=0.0184). Furthermore, an in vitro reporter assay revealed that the -816C construct had significantly higher promoter activity (p