Effect of single nucleotide polymorphisms in the ATP-binding cassette B1 gene on the clini­cal outcome of traumatic brain injury

Abstract

ABSTRACT. The critical role of ATP-binding cassette B1 (ABCB1) in the function of the blood-brain barrier led us to conducted this prospective study in order to investigate the clinical outcome of patients suffering from severe traumatic brain injury. A total of 182 patients with traumatic brain injury were included in our study. Genotyping of ABCB1 C3435T and G2677T/A was conducted using polymerase chain reaction-restriction fragment length polymorphism. Using multivariatelogistic regression analysis, we found that patients carrying the CT+CC genotype of ABCB1 C3435T were more likely to have a better neurological outcome when compared with the TT genotype (odds ratio = 2.71, 95% confidence interval = 1.12-6.86). However, no significant association was found between the G2677T/A polymorphism and outcome of traumatic brain injury patients. Our study provides important information regarding the prognostic value of ABCB1 C3435T, and the ABCB1 C3435T polymorphism may be used as a predictive marker for the outcome of traumatic brain injury patients.

Genetic Influences on Patient-Oriented Outcomes in Traumatic Brain Injury: A Living Systematic Review of Non-Apolipoprotein E Single-Nucleotide Polymorphisms

“…[57][58][59][60][61][62][63][64][65][66][67][68][69][70][71][72][73][80][81][82][83] Study design varied. Fifty-four publications described prospective cohort studies 16,17,[19][20][21][22][23][24][26][27][28][29][30][31]34,35,37,38,[40][41][42][43][44][46][47][48][49][50][51][52][53]…”

“…Ten studies explored the outcome impact of miscellaneous SNPs (which did not fit into the previously mentioned categories) across the spectrum of TBI severity. 58-61,63-65,68,70,80,81 The SNPs studied were related to genes coding for p53, 68 angiotensin-converting enzyme (ACE), 58 neuroglobulin, 63 adenosine triphosphate (ATP) binding cassette, 59,61 aquaporin (AQP)-4, 64 aromatase rs2470144/rs4646/ rs2470152, 65 poly adenosine diphosphate-ribose polymerase-1 (PARP-1) rs3219119/rs3219090, 70 mannose binding lectin-2 (MBL2)/ficolin-2 (FCN2; rs1800451, rs1800450, rs5050737, rs7096206; rs3124953, rs17514136, rs17549193, and rs7851696), 80 and calcineurin (PPP3CC; rs2443504, rs2461491, rs2469749, and rs10108011). 81 Several SNPs were found to be associated with variations in a range of outcomes: p53 arginine homozygotes were found to have a worse GOS at intensive care unit (ICU) discharge; 68 three ACErelated SNPs (C minor allele carriers for rs4461142, C minor allele carriers for rs7221780, and T minor allele carriers for rs8066276) 58 were associated with worse 6-month GOS; neuroglobulin rs3783988 C allele carriers were associated with poor GOS at 3/6/12/24 months 63 ; ATP binding cassette C3435T C allele carriers were associated with worse 6-month GOS 61 ; AQP-4 rs3763043 T homozygotes were associated with worse GOS at 6 months 64 ; aromatase rs2470144 A allele carriers were associated with worse outcome at 6 months; 65 PARP-1 rs3219090 A allele/rs3219119 T allele carriers were associated with poor GOS at 6 months 70 ; and calcineurin PPP3CC rs2443504 AA carriers had increased risk of mortality at 12 months.…”

“…First, a cluster of SNPs related to neurovascular and blood-brain barrier (BBB) function were described. These included: ACE, 57,58 ATP binding cassette, [59][60][61] NOS, and AQP. 64 The ACE and NOS SNPs may play a role in vascular caliber and pre-capillary regulation of cerebral blood flow, whereas the ATP binding cassette protein and AQP are involved in solute transport 59 and water homeostasis 64 across the BBB.…”

Genetics of Chronic Traumatic Encephalopathy

“…Although all of the tauopathies display these tau deposits, the tauopathies are differentiated by the tau isoforms and anatomic distribution. 32 Rare mutations in MAPT cause an autosomal dominant tauopathy (FTDP-17), which may manifest as several clinical phenotypes including frontotemporal dementia COMT, 54,55 ANKK1, 55,56 IL1A, 57 IL1B, 26,58 IL1RN, 59 DRD2, 55,56 TNF, 60 BDNF, [61][62][63] BCL2, 64 mtDNA haplotypes H, J, T, U, 65 mt-ND3, 66 p53, 67 ACE, 68 NGB, 69 ABCB1, 70,103 AQP4, 71 CYP19A1, 72 PARP1, 73 IL6, 74,75 VMAT2 76,77 Genes/loci implicated in poor chronic c outcomes after TBI b APOE4, [78][79][80][81] TMEM106B, 50 BDNF, [61][62][63] mt-ND3, 66 NGB, 69 PPP3CC 105 Genes/loci implicated in AD Early-onset AD: APP, 82 PSEN1, 82 PSEN2, 82 Late-onset AD: CR1, 83,84 INPP5D/SHIP1, 83,84 UNC5C, 85 HBEGF/PFDNI1, 86,87 MEF2C/TMEM161B, 83 TREM2, 88,89 CD2AP/ADGRF2, 83,84 HLA-DRB/HLA-DQB1,…”

The pharmacogenomics of Severe Traumatic Brain Injury

“…They found that ABCB1 rs1045642 (NC 000007.14:g.87509329A>G; AA) and ABCC1 rs4148382 (NC 000016.10:g.16144637G>A; GG) genotypes were associated with lower odds of unfavorable 6-month Glasgow Outcome Scale (GOS) scores, defined as GOS of 1-3 (odds ratio: 0.71 and 0.73, respectively) [15]. The finding with ABCB1 rs1045642 was reversed in a study by Wang et al who studied 182 patients with TBI [16]. They defined favorable outcomes as GOS of 3-5 and found that patients with the (AG, GG) genotypes were more likely to have favorable GOS scores at 6 months post TBI (odds ratio: 2.71) [16].…”