naa a22 4500 510799620 CHVBK 20180411083349.0 cr unu---uuuuu 180411e20131001xx s 000 0 eng 10.1007/s12028-013-9881-7 doi (NATIONALLICENCE)springer-10.1007/s12028-013-9881-7 Influence of ATP-Binding Cassette Polymorphisms on Neurological Outcome After Traumatic Brain Injury [Elektronische Daten] [J'mir Cousar, Yvette Conley, F. Willyerd, Ajit Sarnaik, Ava Puccio, Philip Empey, Patrick Kochanek, Michael Bell, David Okonkwo, Robert Clark] Background: As important mediators of solute transport at the blood-brain and blood-cerebrospinal fluid barriers, ATP-binding cassette (ABC) transporters (including ABCB1, ABCC1, and ABCC2), impact the bioavailability of drugs and endogenous substrates in the brain. While several ABCB1, ABCC1, and ABCC2 single nucleotide polymorphisms (SNPs) have been identified, their impact on outcome after traumatic brain injury (TBI) is unknown. Hypothesis: ABCB1, ABCC1, and ABCC2 SNPs are associated with Glasgow Outcome Scale (GOS) score after TBI. Methods: DNA samples from 305 adult patients with severe TBI (Glasgow Coma Scale, GCS score≤8) were genotyped for tagging SNPs of ABCB1 (rs1045642; rs1128503), ABCC1 (rs212093; rs35621; rs4148382), and ABCC2 (rs2273697). For each SNP, patients were dichotomized based on presence of variant allele for multivariate analysis to determine associations with GOS assigned at 6months adjusting for GCS, Injury Severity score, age, and patient sex. Results: For ABCB1 rs1045642, patients homozygous for the T allele were less likely to be assigned poor outcome versus those possessing the C allele [CT/CC; odds of unfavorable GOS=0.71(0.55-0.92)]. For ABCC1 rs4148382, patients homozygous for the G allele were less likely to be assigned poor outcome versus those possessing the A allele [AG/AA; odds of unfavorable GOS=0.73(0.55-0.98)]. Conclusions: In this single-center study, patients homozygous for the T allele of ABCB1 rs1045642 or the G allele of ABCC1 rs4148382 were found to have better outcome after severe TBI. Further study is necessary to replicate these very preliminary findings and to determine whether these associations are due to central nervous system bioavailability of ABC transporter drug substrates commonly used in the management of TBI, brain efflux of endogenous solutes, or both. Springer Science+Business Media New York, 2013 Blood-brain barrier nationallicence Head trauma nationallicence Membrane transporter nationallicence Multidrug resistance protein nationallicence Multidrug resistance-associated protein nationallicence P-Glycoprotein nationallicence Cousar J'mir Department of Emergency Medicine, University of Cincinnati, 231 Albert Sabin Way, PO Box 670769, 45267-0769, Cincinnati, OH, USA aut Conley Yvette University of Pittsburgh School of Nursing, Victoria 440, 15260, Pittsburgh, PA, USA aut Willyerd F. Children's Hospital of Pittsburgh of UPMC Critical Care Medicine, Safar Center for Resuscitation Research, 4401 Penn Ave Faculty Pavillion Suite 02000, 15224, Pittsburgh, PA, USA aut Sarnaik Ajit University Pediatricians, 4201 St. Antoine, UHC-6F, Mailbox #226, 48201, Detroit, MI, USA aut Puccio Ava Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop St, 15213, Pittsburgh, PA, USA aut Empey Philip Department of Pharmacy & Therapeutics, University of Pittsburgh School of Pharmacy, 3501 Terrace St., 805 Salk Hall, 15261, Pittsburgh, PA, USA aut Kochanek Patrick Departments of Critical Care Medicine, Pediatrics, and Anesthesiology, Safar Center for Resuscitation Research, 3434 Fifth Avenue, 15260, Pittsburgh, PA, USA aut Bell Michael Departments of Critical Care Medicine and Neurological Surgery, University of Pittsburgh School of Medicine, 4401 Penn Avenue, 15224, Pittsburgh, PA, USA aut Okonkwo David Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop St, 15213, Pittsburgh, PA, USA aut Clark Robert Safar Center for Resuscitation Research, 3434 Fifth Avenue, 15260, Pittsburgh, PA, USA aut Neurocritical Care Springer US; http://www.springer-ny.com 19/2(2013-10-01), 192-198 1541-6933 19:2<192 2013 19 12028 https://doi.org/10.1007/s12028-013-9881-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s12028-013-9881-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cousar J'mir Department of Emergency Medicine, University of Cincinnati, 231 Albert Sabin Way, PO Box 670769, 45267-0769, Cincinnati, OH, USA aut NATIONALLICENCE 700 1- Conley Yvette University of Pittsburgh School of Nursing, Victoria 440, 15260, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Willyerd F. Children's Hospital of Pittsburgh of UPMC Critical Care Medicine, Safar Center for Resuscitation Research, 4401 Penn Ave Faculty Pavillion Suite 02000, 15224, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Sarnaik Ajit University Pediatricians, 4201 St. Antoine, UHC-6F, Mailbox #226, 48201, Detroit, MI, USA aut NATIONALLICENCE 700 1- Puccio Ava Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop St, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Empey Philip Department of Pharmacy & Therapeutics, University of Pittsburgh School of Pharmacy, 3501 Terrace St., 805 Salk Hall, 15261, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Kochanek Patrick Departments of Critical Care Medicine, Pediatrics, and Anesthesiology, Safar Center for Resuscitation Research, 3434 Fifth Avenue, 15260, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Bell Michael Departments of Critical Care Medicine and Neurological Surgery, University of Pittsburgh School of Medicine, 4401 Penn Avenue, 15224, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Okonkwo David Department of Neurological Surgery, University of Pittsburgh School of Medicine, 200 Lothrop St, 15213, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Clark Robert Safar Center for Resuscitation Research, 3434 Fifth Avenue, 15260, Pittsburgh, PA, USA aut NATIONALLICENCE 773 0- Neurocritical Care Springer US; http://www.springer-ny.com 19/2(2013-10-01), 192-198 1541-6933 19:2<192 2013 19 12028 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer