title: 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.
authors.affiliation: 1 Department of Neurology, Laboratory of Neurogenetics, University of Thessaly , University Hospital of Larissa, Larissa, Greece .
authors.forename: Efthimios
authors.initials: E
authors.lastname: Dardiotis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Paterakis
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsivgoulis
authors.forename: Magdalini
authors.initials: M
authors.lastname: Tsintou
authors.forename: Georgios F
authors.initials: GF
authors.lastname: Hadjigeorgiou
authors.forename: Maria
authors.initials: M
authors.lastname: Dardioti
authors.forename: Savas
authors.initials: S
authors.lastname: Grigoriadis
authors.forename: Constantina
authors.initials: C
authors.lastname: Simeonidou
authors.forename: Apostolos
authors.initials: A
authors.lastname: Komnos
authors.forename: Eftychia
authors.initials: E
authors.lastname: Kapsalaki
authors.forename: Kostas
authors.initials: K
authors.lastname: Fountas
authors.forename: Georgios M
authors.initials: GM
authors.lastname: Hadjigeorgiou
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D051401:Aquaporin 4 / Q000235:genetics*; D001930:Brain Injuries / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D020127:Recovery of Function / Q000235:genetics; D055815:Young Adult
chemical_list: D051401:Aquaporin 4
keywords: AQP4; genetics; polymorphism; tag SNPs; traumatic brain injury