Research Reports - Influence of ATP-Binding cassette polymorphisms on neurological outcome after traumatic brain injury
Neurocrit Care. 2013 Jul 30
Cousar JL, Conley YP, Willyerd FA, Sarnaik AA, Puccio AM, Empey PE, Kochanek PM, Bell MJ, Okonkwo DO, Clark RS
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 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