Dataset Information

AQP4 tag single nucleotide polymorphisms in patients with traumatic brain injury.

ABSTRACT: Accumulating evidence suggests that the extent of brain injury and the clinical outcome after traumatic brain injury (TBI) are modulated, to some degree, by genetic variants. Aquaporin-4 (AQP4) is the predominant water channel in the central nervous system and plays a critical role in controlling the water content of brain cells and the development of brain edema after TBI. We sought to investigate the influence of the AQP4 gene region on patient outcome after TBI by genotyping tag single nucleotide polymorphisms (SNPs) along AQP4 gene. A total of 363 patients with TBI (19.6% female) were prospectively evaluated. Data including the Glasgow Coma Scale (GCS) scores at admission, the presence of intracranial hemorrhage, and the 6-month Glasgow Outcome Scale (GOS) scores were collected. Seven tag SNPs across the AQP4 gene were identified based on the HapMap data. Using logistic regression analyses, SNPs and haplotypes were tested for associations with 6-month GOS after adjusting for age, GCS score, and sex. Significant associations with TBI outcome were detected for rs3763043 (OR [95% confidence interval (CI)]: 5.15 [1.60-16.5], p=0.006, for recessive model), rs3875089 (OR [95% CI]: 0.18 [0.07-0.50] p=0.0009, for allele difference model), and a common haplotype of AQP4 tag SNPs (OR [95% CI]: 2.94, [1.34-6.36], p=0.0065). AQP4 tag SNPs were not found to influence the initial severity of TBI or the presence of intracranial hemorrhages. In conclusion, the present study provides evidence for possible involvement of genetic variations in AQP4 gene in the functional outcome of patients with TBI.

SUBMITTER: Dardiotis E

PROVIDER: S-EPMC4238262 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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AQP4 tag single nucleotide polymorphisms in patients with traumatic brain injury.

Dardiotis Efthimios E Paterakis Konstantinos K Tsivgoulis Georgios G Tsintou Magdalini M Hadjigeorgiou Georgios F GF Dardioti Maria M Grigoriadis Savas S Simeonidou Constantina C Komnos Apostolos A Kapsalaki Eftychia E Fountas Kostas K Hadjigeorgiou Georgios M GM

Journal of neurotrauma 20141010 23

Accumulating evidence suggests that the extent of brain injury and the clinical outcome after traumatic brain injury (TBI) are modulated, to some degree, by genetic variants. Aquaporin-4 (AQP4) is the predominant water channel in the central nervous system and plays a critical role in controlling the water content of brain cells and the development of brain edema after TBI. We sought to investigate the influence of the AQP4 gene region on patient outcome after TBI by genotyping tag single nucleo ...[more]

PMID: 24999750

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Project description:BACKGROUND: Single nucleotide polymorphisms (SNPs), the most abundant variations in a genome, have been widely used in various studies. Detection and characterization of citrus haplotype-based expressed sequence tag (EST) SNPs will greatly facilitate further utilization of these gene-based resources. RESULTS: In this paper, haplotype-based SNPs were mined out of publicly available citrus expressed sequence tags (ESTs) from different citrus cultivars (genotypes) individually and collectively for comparison. There were a total of 567,297 ESTs belonging to 27 cultivars in varying numbers and consequentially yielding different numbers of haplotype-based quality SNPs. Sweet orange (SO) had the most (213,830) ESTs, generating 11,182 quality SNPs in 3,327 out of 4,228 usable contigs. Summed from all the individually mining results, a total of 25,417 quality SNPs were discovered - 15,010 (59.1%) were transitions (AG and CT), 9,114 (35.9%) were transversions (AC, GT, CG, and AT), and 1,293 (5.0%) were insertion/deletions (indels). A vast majority of SNP-containing contigs consisted of only 2 haplotypes, as expected, but the percentages of 2 haplotype contigs varied widely in these citrus cultivars. BLAST of the 25,417 25-mer SNP oligos to the Clementine reference genome scaffolds revealed 2,947 SNPs had "no hits found", 19,943 had 1 unique hit / alignment, 1,571 had one hit and 2+ alignments per hit, and 956 had 2+ hits and 1+ alignment per hit. Of the total 24,293 scaffold hits, 23,955 (98.6%) were on the main scaffolds 1 to 9, and only 338 were on 87 minor scaffolds. Most alignments had 100% (25/25) or 96% (24/25) nucleotide identities, accounting for 93% of all the alignments. Considering almost all the nucleotide discrepancies in the 24/25 alignments were at the SNP sites, it served well as in silico validation of these SNPs, in addition to and consistent with the rate (81%) validated by sequencing and SNaPshot assay. CONCLUSIONS: High-quality EST-SNPs from different citrus genotypes were detected, and compared to estimate the heterozygosity of each genome. All the SNP oligo sequences were aligned with the Clementine citrus genome to determine their distribution and uniqueness and for in silico validation, in addition to SNaPshot and sequencing validation of selected SNPs.

Project description:Emotional distress is a common, but poorly addressed, feature of moderate-severe traumatic brain injury (TBI). Previously identified sociodemographic, psychological, and injury-related factors account for only a small proportion of the variability in emotional distress post-TBI. Genetic factors may help to further understand emotional distress in this population. The catechol-O-methyltransferase (COMT) Val158 and brain-derived neurotrophic factor (BDNF) 66Met single-nucleotide polymorphisms (SNPs) have been identified as possible contributory factors to outcomes after TBI. We investigated whether the COMT Val158 and BDNF 66Met SNPs were associated with emotional distress 1 year after moderate-severe TBI, and whether these associations were moderated by age, sex, and TBI severity (as measured by the duration of post-traumatic amnesia [PTA]). Moderate-severe TBI survivors (COMT, n = 391; BDNF, n = 311) provided saliva samples after admission to a TBI rehabilitation hospital. At a follow-up interview ∼1 year after injury, participants completed a self-report measure of emotional distress (Hospital Anxiety and Depression Scale; HADS). Multiple linear regression models were constructed for each SNP to predict total scores on the HADS. Neither COMT Val158 nor BDNF 66Met carriage status (carrier vs. non-carrier) significantly predicted emotional distress (COMT, p = 0.49; BDNF, p = 0.66). Interactions of SNP × age (COMT, p = 0.90; BDNF, p = 0.93), SNP × sex (COMT, p = 0.09; BDNF, p = 0.60), SNP × injury severity (COMT, p = 0.53; BDNF, p = 0.87), and SNP × sex × age (COMT, p = 0.08; BDNF, p = 0.76) were also non-significant. Our null findings suggest that COMT Val158 and BDNF 66Met SNPs do not aid the prediction of emotional distress 1 year after moderate-severe TBI, neither in isolation nor in interaction with age, sex and injury severity. The reporting of null findings such as ours is important to avoid publication bias and prompt researchers to consider the challenges of single-gene candidate studies in understanding post-TBI outcomes. Analyses in larger samples that incorporate multiple genetic factors and their relevant moderating factors may provide a greater understanding of the role of genetics in post-TBI emotional distress.

Project description:ObjectiveThe two objectives of this study were (1) to replicate the previous finding that a single nucleotide polymorphism (SNP) in the ANKK1 gene (SNP rs1800497 formerly known as the DRD2 TAQ1 A allele) is associated with measures of learning and response latency after traumatic brain injury (TBI) and (2) to further characterize the genetic basis of the effect by testing the strength of association and degree of linkage disequilibrium between the cognitive outcome measures and a selected ensemble of 31 polymorphisms from three adjacent genes in the region of rs1800497.MethodA cohort of 54 patients with TBI and 21 comparison subjects were genotyped for the DRD2 TAQ1 A polymorphism (rs1800497). Ninety-three patients with TBI and 48 comparison subjects (the current cohort and an earlier independent cohort) were also genotyped for 31 additional neighbouring polymorphisms in NCAM, ANKK1 and DRD2. TBI patients were studied 1 month after injury. All subjects completed memory and attention tests, including the California Verbal Learning Test (CVLT) recognition task and the Gordon Continuous Performance Test (CPT).ResultsAs in a previous study the T allele of TAQ1 A (rs1800497) was associated with poorer performance on the CVLT recognition trial in both TBI and control subjects. There was also a significant diagnosis-by-allele interaction on CPT measures of response latency, largely driven by slower performance in the TBI participants with the T allele. Analysis of 31 additional neighbouring polymorphisms from NCAM, ANKK1 and DRD2 in the TBI patients showed four haploblocks. A haploblock of three SNPs in ANKK1 (rs11604671, rs4938016 and rs1800497 (TAQ1A)) showed the greatest association with cognitive outcome measures.ConclusionsThe results confirm a previously published association between the TAQ1 A (rs1800497) T allele and cognitive outcome measures 1 month after TBI and suggest that a haploblock of polymorphisms in ANKK1, rather than the adjacent DRD2 gene, has the highest association with these measures after TBI.

Dataset Information

AQP4 tag single nucleotide polymorphisms in patients with traumatic brain injury.

Publications

AQP4 tag single nucleotide polymorphisms in patients with traumatic brain injury.

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