title: Leveraging an Electronic Health Record-Linked Biorepository to Generate a Metformin Pharmacogenomics Hypothesis.
abstract: Metformin is a first-line antihyperglycemic agent commonly prescribed in type 2 diabetes mellitus (T2DM), but whose pharmacogenomics are not clearly understood. Further, due to accumulating evidence highlighting the potential for metformin in cancer prevention and treatment efforts it is imperative to understand molecular mechanisms of metformin. In this electronic health record(EHR)-based study we explore the potential association of the flavin-containing monooxygenase(FMO)-5 gene, a biologically plausible biotransformer of metformin, and modifying glycemic response to metformin treatment. Using a cohort of 258 T2DM patients who had new metformin exposure, existing genetic data, and longitudinal electronic health records, we compared genetic variation within FMO5 to change in glycemic response. Gene-level and SNP-level analysis identified marginally significant associations for FMO5 variation, representing an EHR-driven pharmacogenetics hypothesis for a potential novel mechanism for metformin biotransformation. However, functional validation of this EHR-based hypothesis is necessary to ascertain its clinical and biological significance.
authors: Mayo Clinic, Rochester, MN ; University of Minnesota, Minneapolis, MN.
authors: Matthew K
authors: MK
authors: Breitenstein
authors: Mayo Clinic, Rochester, MN.
authors: Liewei
authors: L
authors: Wang
authors: University of Minnesota, Minneapolis, MN.
authors: Gyorgy
authors: G
authors: Simon
authors: Mayo Clinic, Rochester, MN.
authors: Euijung
authors: E
authors: Ryu
authors: Mayo Clinic, Rochester, MN.
authors: Sebastian M
authors: SM
authors: Armasu
authors: Mayo Clinic, Rochester, MN.
authors: Balmiki
authors: B
authors: Ray
authors: Mayo Clinic, Rochester, MN.
authors: Richard M
authors: RM
authors: Weinshilboum
authors: Mayo Clinic, Rochester, MN.
authors: Jyotishman
authors: J
authors: Pathak