title: Effect of angiotensin-converting enzyme tag single nucleotide polymorphisms on the outcome of patients with traumatic brain injury.
abstract: BACKGROUND
  Genetic variants appear to influence, at least to some degree, the extent of brain injury and the clinical outcome of patients who have sustained a traumatic brain injury (TBI). Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase that is implicated in the regulation of blood pressure and cerebral circulation. ACE gene polymorphisms were found to regulate serum ACE enzyme activity.
  
  
  OBJECTIVE
  The present study aimed to investigate possible influence of ACE gene region variants on patients' outcome after TBI.
  
  
  METHODS
  In total, 363 TBI patients prospectively enrolled in the study were genotyped for five tag single nucleotide polymorphisms (SNPs) across the ACE gene. Using logistic regression analyses, tag SNPs and their constructed haplotypes were tested for associations with 6-month Glasgow Outcome Scale scores, after adjustment for age, sex, Glasgow Coma Scale scores at admission, and the presence of a hemorrhagic event in the initial computed tomography scan.
  
  
  RESULTS
  Significant effects on TBI outcome were found for three neighboring tag SNPs in the codominant (genotypic) model of inheritance [rs4461142: odds ratio (OR) 0.26, 95% confidence interval (CI) 0.12-0.57, P = 0.0001; rs7221780: OR 2.67, 95% CI 1.25-5.72, P = 0.0003; and rs8066276: OR 3.82, 95% CI 1.80-8.13, P = 0.0002; for the heterozygous variants compared with the common alleles]. None of the constructed common tag SNPs haplotypes was associated with TBI outcome.
  
  
  CONCLUSIONS
  The present study provides evidence of the possible influence of genetic variations in a specific region of the ACE gene on the outcome of TBI patients. This association may have pharmacogenetic implications in identifying those TBI patients who may benefit from ACE inhibition.
authors.affiliation: aLaboratory of Neurogenetics, Department of Neurology bDepartment of Neurosurgery, Faculty of Medicine, University Hospital of Larissa, University of Thessaly cIntensive Care Unit, General Hospital of Larissa dDepartment of Radiology, School of Medicine, University of Thessaly, Larissa eSecond Department of Neurology, School of Medicine, 'Attikon' University Hospital, University of Athens, Athens fSecond Department of Neurosurgery, Hippokration University Hospital gDepartment of Physiology, Aristotle University of Thessaloniki, Thessaloniki, Greece hInternational Clinical Research Center, St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Efthimios
authors.initials: E
authors.lastname: Dardiotis
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Paterakis
authors.forename: Vasileios
authors.initials: V
authors.lastname: Siokas
authors.forename: Georgios
authors.initials: G
authors.lastname: Tsivgoulis
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; D001930:Brain Injuries / Q000235:genetics*; D003710:Demography; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056426:Genetic Loci; D015600:Glasgow Coma Scale; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A