Published online February 1, 2007
PEDIATRICS Vol. 119 No. 2 February 2007, pp. 306-313 (doi:10.1542/10.1542/peds.2006-1083)
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ARTICLE

Association of Apolipoprotein E Genotype and Cerebral Palsy in Children

Maxine M. Kuroda, PhD, MPHa, Mary E. Weck, PTb, John F. Sarwark, MDc, Aaliyah Hamidullah, BSca and Mark S. Wainwright, MD, PhDa,d,e

a Department of Pediatrics, Division of Neurology
b Department of Physical Therapy, Division of Rehabilitative Services
c Department of Orthopedic Surgery
d Department of Molecular Pharmacology and Biological Chemistry
e Center for Drug Discovery and Chemical Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois

OBJECTIVES. We tested the hypotheses that apolipoprotein E genotype, in particular carriage of the {varepsilon}4 allele, is more likely to be associated with cerebral palsy and that children with more severe neurologic impairment are more likely to carry this allele.

METHODS. In this cross-sectional study, 209 children with cerebral palsy were matched with healthy control subjects according to gender and race. Diagnosis of cerebral palsy was confirmed through physician consultation, medical chart review, and parent interview. Apolipoprotein E genotyping was performed with DNA obtained with buccal swabs. Severity of motor impairment was rated by physical therapists, and occipitofrontal circumference was measured.

RESULTS. Compared with gender- and race-matched control subjects, overall risk for cerebral palsy was elevated 3.4-fold among children carrying an {varepsilon}4 allele and was particularly elevated for children with quadriplegia/triplegia. This finding was independent of birth weight. Carriage of the {varepsilon}4 allele was also associated with increased severity of cerebral palsy and with a trend toward increased likelihood for microcephaly. Moreover, children carrying an {varepsilon}2 allele were at greater risk for cerebral palsy.

CONCLUSIONS. These data implicate the apolipoprotein E {varepsilon}4 and {varepsilon}2 genotypes as susceptibility factors in determining neurologic outcomes after perinatal brain injury. Additional studies are warranted to establish the role of apolipoprotein E in specific pathogenetic pathways leading to cerebral palsy or poor neurologic outcomes after perinatal brain injury.

Key Words: cerebral palsy • apolipoprotein E • genotype

Abbreviations: CP—cerebral palsy • apoE—apolipoprotein E • AD—Alzheimer disease • OFC—occipitofrontal circumference • OR—odds ratio • CI—confidence interval

Accepted Sep 28, 2006.


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