title: Influence of ATP-binding cassette polymorphisms on neurological outcome after traumatic brain injury.
abstract: 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.
  
  
  OBJECTIVE
  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 6 months 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.
authors.affiliation: Department of Emergency Medicine, University of Cincinnati, 231 Albert Sabin Way, PO Box 670769, Cincinnati, OH, 45267-0769, USA, cousarjr@uc.edu.
authors.forename: J'mir L
authors.initials: JL
authors.lastname: Cousar
authors.forename: Yvette P
authors.initials: YP
authors.lastname: Conley
authors.forename: F Anthony
authors.initials: FA
authors.lastname: Willyerd
authors.forename: Ajit A
authors.initials: AA
authors.lastname: Sarnaik
authors.forename: Ava M
authors.initials: AM
authors.lastname: Puccio
authors.forename: Philip E
authors.initials: PE
authors.lastname: Empey
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bell
authors.forename: David O
authors.initials: DO
authors.lastname: Okonkwo
authors.forename: Robert S B
authors.initials: RS
authors.lastname: Clark
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D001812:Blood-Brain Barrier / Q000502:physiology; D001930:Brain Injuries / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015600:Glasgow Coma Scale; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D020127:Recovery of Function / Q000235:genetics; D055815:Young Adult
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C513055:ABCB1 protein, human; C000715087:ABCC2 protein, human; C421109:multidrug resistance-associated protein 1
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