title: Genes determining the severity of cerebral palsy: the role of single nucleotide polymorphisms on the amount and structure of apolipoprotein E.
abstract: OBJECTIVE
  Apolipoprotein E (apoE) influences repair and other processes in the brain, and the apoE4 variant is a risk factor for Alzheimer's disease and for prolonged recovery following traumatic brain injury. We previously reported that specific single nucleotide polymorphisms in the APOE or TOMM40 genes affecting the structure and production of apoE were associated with epilepsy, more impaired hand function and gastrostomy tube feeding in children with cerebral palsy (CP). This study explored how various combinations of the same polymorphisms may affect these clinical manifestations.
  
  
  METHODS
  Successful DNA analyses of APOE and TOMM40 were carried out on 227 children. The CP Register of Norway provided details of gross and fine motor function, epilepsy and gastrostomy tube feeding. Possible associations between these clinical manifestations and various combinations of the APOEε2, ε3 or ε4 alleles and of the rs59007384 polymorphism in the TOMM40 gene were explored.
  
  
  RESULTS
  Epilepsy, impaired fine motor function and gastrostomy tube feeding were less common in children carrying the combination of rs59007384 GG and APOEε2 or ε3 than in children with other combinations.
  
  
  CONCLUSIONS
  Our findings suggest that specific combinations of genes influence the structure and production of apoE differently and affect the clinical manifestations of CP.
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.|Department of Pediatrics, St. Olavs Hospital, University Hospital of Trondheim, Trondheim, Norway.
authors.forename: Espen
authors.initials: E
authors.lastname: Lien
authors.affiliation: Vestfold Hospital Trust, Cerebral Palsy Register of Norway, Tønsberg, Norway.
authors.forename: Guro
authors.initials: G
authors.lastname: Andersen
authors.affiliation: DNA Science Core, University of Virginia School of Medicine, Charlottesville, VA, USA.
authors.forename: Yongde
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Research Center for Genetic Medicine, Children's National Medical Center, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Gordish-Dressman
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Jon S
authors.initials: JS
authors.lastname: Skranes
authors.affiliation: Department of Pediatrics, University of Virginia, Charlottesville, VA, USA.|Cerebral Palsy International Research Foundation, New York, NY, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Blackman
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Torstein
authors.initials: T
authors.lastname: Vik
mesh_terms: D001057:Apolipoproteins E / Q000235:genetics*; D002547:Cerebral Palsy / Q000150:complications / Q000235:genetics* / Q000628:therapy; D002648:Child; D004750:Enteral Nutrition; D004827:Epilepsy / Q000235:genetics; D005260:Female; D005774:Gastrostomy; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009048:Motor Skills / Q000502:physiology; D009664:Norway; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D001057:Apolipoproteins E; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human
keywords: APOE; Cerebral palsy; Regulation of apoE synthesis; apoE; rs59007384 polymorphism