Browsing by Subject "genetic"

Now showing 1 - 4 of 4
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    AMPD1 polymorphism and response to regadenoson
    (Future Medicine, 2015-11) Saab, Rayan; Zouk, Aline N.; Mastouri, Ronald; Skaar, Todd C.; Philips, Santosh; Kreutz, Rolf P.; Department of Medicine, IU School of Medicine
    AIMS: AMPD1 c.34C > T (rs17602729) polymorphism results in AMPD1 deficiency. We examined the association of AMPD1 deficiency and variability of hemodynamic response to regadenoson. SUBJECTS & METHODS: Genotyping for c.34C>T was performed in 267 patients undergoing regadenoson cardiac stress testing. RESULTS: Carriers of c.34C >T variant exhibited higher relative changes in systolic blood pressure (SBP) compared with wild-type subjects ([%] SBP change to peak: 12 ± 25 vs 5 ± 13%; p = 0.01) ([%] SBP change to nadir: -3 ± 15 vs -7 ± 11%; p = 0.04). Change in heart rate was similar between groups, but side effects were more common in carriers of the variant (+LR = 4.2; p = 0.04). CONCLUSION: AMPD1 deficiency may be involved in the modulation of regadenoson's systemic effects.
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    Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3 variants
    (Future Medicine, 2019-09-27) Sadhasivam, Senthilkumar; Henker, Richard A.; Brandom, Barbara W.; McAuliffe, John J.; Anesthesia, School of Medicine
    Aim: Identify variants in RYR1, CACNA1S and STAC3, and predict malignant hyperthermia (MH) pathogenicity using Bayesian statistics in individuals clinically treated as MH susceptible (MHS). Materials & methods: Whole exome sequencing including RYR1, CACNA1S and STAC3 performed on 64 subjects with: MHS; suspected MH event or first-degree relative; and MH negative. Variant pathogenicity was estimated using in silico analysis, allele frequency and prior data to calculate Bayesian posterior probabilities. Results: Bayesian statistics predicted CACNA1S variant p.Thr1009Lys and RYR1 variants p.Ser1728Phe and p.Leu4824Pro are likely pathogenic, and novel STAC3 variant p.Met187Thr has uncertain significance. Nearly a third of MHS subjects had only benign variants. Conclusion: Bayesian method provides new approach to predict MH pathogenicity of genetic variants.
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    Common genetic polymorphisms of adenosine A2A receptor do not influence response to regadenoson
    (Future Science, 2017-04) Berlacher, Mark; Mastouri, Ronald; Philips, Santosh; Skaar, Todd C.; Kreutz, Rolf P.; Medicine, School of Medicine
    Aim: Hemodynamic response to regadenoson varies greatly, and underlying mechanisms for variability are poorly understood. We hypothesized that five common variants of adenosine A2A receptor (ADORA2A) are associated with altered response to regadenoson. Methods: Consecutive subjects (n = 357) undergoing resting regadenoson nuclear stress imaging were enrolled. Genotyping was performed using Taqman-based assays for rs5751862, rs2298383, rs3761422, rs2267076 and rs5751876. Results: There was no significant difference in heart rate or blood pressure between different genotypes following regadenoson administration. There was also no significant difference in myocardial ischemia detected by nuclear perfusion imaging as defined by summed difference score, or in self-reported side effects among the genotypes tested. Conclusion: The common A2A variants studied are not associated with variability in hemodynamic response to regadenoson or variability in detection of ischemia with nuclear perfusion stress imaging.
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    The Direct Reprogramming of Somatic Cells: Establishment of a Novel System for Photoreceptor Derivation
    (2013-08-22) Steward, Melissa Mary; Meyer, Jason S.; Dai, Guoli; Randall, Stephen Karl, 1953-; Atkinson, Simon
    Photoreceptors are a class of sensory neuronal cells that are deleteriously affected in many disorders and injuries of the visual system. Significant injury or loss of these cells often results in a partial or complete loss of vision. While previous studies have determined many necessary components of the gene regulatory network governing the establishment, development, and maintenance of these cells, the necessary and sufficient profile and timecourse of gene expression and/or silencing has yet to be elucidated. Arduous protocols do exist to derive photoreceptors in vitro utilizing pluripotent stem cells, but only recently have been able to yield cells that are disease- and/or patient-specific. The discovery that mammalian somatic cells can be directly reprogrammed to another terminally-differentiated cell phenotype has inspired an explosion of research demonstrating the successful genetic reprogramming of one cell type to another, a process which is typically both more timely and efficient than those used to derive the same cells from pluripotent stem cell sources. Therefore, the emphasis of this study was to establish a novel system to be used to determine a minimal transcriptional network capable of directly reprogramming mouse embryonic fibroblasts (MEFs) to rod photoreceptors. The tools, assays, and experimental design chosen and established herein were designed and characterized to facilitate this determination, and preliminary data demonstrated the utility of this approach for accomplishing this aim.