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

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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.