ATORVASTATIN ON PLASMA CHOLINE CONCENTRATION IN SUBJECTS WITH AND WITHOUT THE ME

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目的： 本研究旨在探讨阿托伐他汀对高血压患者和非高血压患者血浆胆碱浓度的影响。 亚甲基四氢叶酸还原酶1(MTHFD1)基因G1958A等位基因。 参与者： 这项研究将在18-75岁的健康男性中进行，这些男性没有他汀类药物不耐受的已知危险因素。 程序(方法)： 将对60名受试者进行亚甲基四氢叶酸脱氢酶1(MTHFD1)基因G1958A多态性的筛查。将根据是否存在多态来选择25名受试者。将努力反映当地的人口统计数据。受试者将在五周内接受胆碱含量稳定但不受限制的饮食。在研究的中间三周(第二周到第四周)，受试者将每天服用阿托伐他汀，剂量递增：每天10毫克，持续一周，每天20毫克，持续一周，每天40毫克，持续一周。受试者将每周进行检查和面谈，以筛选肌病的体征和症状；每周禁食采集血液样本，以测量血清ALT、血清CK和血浆胆碱。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Purpose: This study is to determine the effect of atorvastatin on plasma choline concentration in humans with and without the G1958A allele of the methylenetetrahydrofolate reductase 1 (MTHFD1) gene. Participants: The study will be conducted on healthy males aged 18-75 without known risk factors for statin intolerance. Procedures (methods): 60 subjects will be screened for the G1958A polymorphism of the gene for methylenetetrahydrofolate dehydrogenase 1 (MTHFD1). 25 subjects will be chosen based on presence or absence of the polymorphism. Efforts will be made to reflect local demographics. Subjects will be fed a diet with a consistent, but not restricted, choline content for five weeks. In the middle three weeks of the study (weeks two through four), subjects will be administered atorvastatin daily at an escalating dose: 10 mg daily for one week, 20 mg daily for one week, and 40mg daily for one week. Subjects will have weekly exams and interviews to screen for signs and symptoms of myopathy; and weekly fasting collection of blood samples for measurement of serum ALT, serum CK, and plasma choline.