Gene sequences regulating the production of apoE and cerebral palsy of variable severity.
BACKGROUND
The apoE protein is the most important lipid transporter in the brain and has also been shown to have several regulatory functions in the central nervous system. The production of apoE is regulated by a number of genes and increases under certain conditions such as cerebral injury in adults.


OBJECTIVE
Our aim was to study whether variations in genes regulating the expression of the APOE gene were associated with severity of cerebral palsy (CP).


METHODS
Children enrolled in the Cerebral Palsy Register of Norway (CPRN) were invited to participate in this cross-sectional study; 281 of the invited 703 children (40%) returned swabs with buccal cells collected by parents. Six genetic variations thought to affect the production of apoE were genotyped and correlated with clinical data recorded in the CPRN.


RESULTS
Compared with children carrying the GG allele, children with genotype GT or TT in a specific genetic variation (rs59007384 located in the nearby TOMM40 gene) had excess risk for worse fine motor function (Odds ratio (OR): 1.82; 95% Confidence interval (CI): 1.10-2.99; p = 0.019) and epilepsy (OR: 2.32; CI: 1.17-4.61; p = 0.016). There was no association between severity of CP and any of the other five genetic variations analyzed.


CONCLUSIONS
Our findings suggest that genetic variations in one of the sequences regulating the expression of APOE, may be associated with worse clinical outcome in children with cerebral palsy.
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. Electronic address: espen.lien@ntnu.no.
Espen
E
Lien
Vestfold Hospital Trust, The Cerebral Palsy Register of Norway, Tønsberg, Norway.
Guro L
GL
Andersen
DNA Science Core, Univ. of Virginia School of Medicine, Charlottesville, VA, USA.
Yongde
Y
Bao
George Washington University School of Medicine and Health Sciences, Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
Heather
H
Gordish-Dressman
Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Jon
J
Skranes
Department of Pediatrics, University of Virginia, Charlottesville, VA, USA; Cerebral Palsy International Research Foundation, Princeton Junction, NJ, USA.
James A
JA
Blackman
Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Torstein
T
Vik
D000293:Adolescent; D001057:Apolipoproteins E / Q000235:genetics* / Q000378:metabolism*; D002547:Cerebral Palsy / Q000150:complications / Q000235:genetics*; D002648:Child; D004252:DNA Mutational Analysis; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009069:Movement Disorders / Q000209:etiology; D009664:Norway; D016017:Odds Ratio; D012189:Retrospective Studies
D001057:Apolipoproteins E; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human
APOE; APOE regulator genes; Severity of CP