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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 目的： 本研究旨在确定阿托伐他汀对有和无阿托伐他汀治疗的人血浆胆碱浓度的影响。 亚甲基四氢叶酸还原酶1（MTHFD 1）基因的G1958 A等位基因。 参会人员： 该研究将在年龄为18-75岁的健康男性中进行，没有已知的他汀类药物不耐受风险因素。 程序（方法）： 将筛选60例受试者的亚甲基四氢叶酸脱氢酶1（MTHFD 1）基因的G1958 A多态性。将根据多态性的存在或不存在选择25名受试者。 将努力反映当地的人口情况。受试者将被喂食具有一致但不受限制的胆碱含量的饮食五周。在研究的中间三周（第2 - 4周），受试者将每天接受阿托伐他汀给药，剂量递增：每天10 mg，持续一周;每天20 mg，持续一周;每天40 mg，持续一周。受试者将接受每周一次的检查和访谈，以筛查肌病的体征和症状;每周空腹采集血样，用于测量血清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.