Postoperative morbidity and mortality is an under-recognized, yet significant public health problem. In 2004. 1.4% of all inpatients died after surgery. Myocardial infarction is a major contributor to postoperative mortality. Perioperative (pharmaco-)genetics may reduce adverse outcomes by individualizing therapeutic options and drug therapy (personalized medicine). However, there is currently a significant paucity of Studies investigating the potential benefits of perioperative pharmacogenetics. This K23 proposal is for a career development program in perioperative pharmacogenetics. The research component centers on a randomized blinded controlled trial investigating the association between gene variants in intermediary metabolic pathways known to be altered by nitrous oxide and postoperative myocardial ischemia. Nitrous oxide is the most commonly used general anesthetic in the world. It inhibits vitamin 812 and increase homocysteine concentrations. Chronic homocysteinemia has been associated with adverse cardiac events.The MTHFR 677 C>T polymorphism is the most important genetic determinant for elevated homocysteine and is also associated with significantly higher homocysteine after nitrous oxide anesthesia. Thus, this investigation will test the hypothesis that patients with this gene variant have a higher incidence of postoperative myocardial ischemia after nitrous oxide, anesthesia than wild-type patients (aim 1). We will also determine if this risk can be ameliorated by blinded, randomized perioperative supplementation of vitamin B12 and folate (aim 2). The trial will target patients at high risk for cardiac events undergoing major noncardiac surgery. The didactic training component of the K23 proposal will be the Masters of Science program in Genetic Epidemiology. The overall long-term career objective is to become an independent investigator in perioperative pharmacogenetics.2013-12-31NIHNAGELE, PETER2010-01-04Perioperative pharmacogenetics: Nitrous oxide and anesthetic outcomesK23GM087534prns:endDateend dateprns:fullNamefull nameprns:grantAwardedBygrant awarded byprns:isPrimaryPositionis primary positionprns:latitudelatitudeprns:longitudelongitudeprns:mainImagephotoprns:personIdPerson IDprns:personInPrimaryPositionperson in primary positionprns:positionInDepartmentposition in departmentprns:principalInvestigatorNameprincipal investigator nameprns:sortOrdersort orderprns:startDatestart datebibo:abstractabstractAgreementvivo:contributingRolecontributorDepartmentGrantvivo:hrJobTitleHR job titlePositionvivo:positionInOrganizationposition in organizationvivo:preferredTitlepreferred titleResearcher Rolevivo:researcherRoleOfresearcher role ofRolevivo:roleContributesTocontributes tovivo:sponsorAwardIdsponsor award idrdf:typetyperdfs:labellabelAgentfoaf:firstNamefirst namefoaf:lastNamelast nameOrganizationPersonPeterNagelePeter Nagele41.7886000000000087.598699999999993590Nagele, PeterProfessorAnesthesia and Critical CarePrincipal InvestigatorUniversity of Chicagotrue1ProfessorProfessor