Association of apolipoprotein E genotype and cerebral palsy in children

OBJECTIVES. We tested the hypotheses that apolipoprotein E genotype, in particular carriage of the ε4 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 ε4 allele and was particularly elevated for children with quadriplegia/triplegia. This finding was independent of birth weight. Carriage of the ε4 allele was also associated with increased severity of cerebral palsy and with a trend toward increased likelihood for microcephaly. Moreover, children carrying an ε2 allele were at greater risk for cerebral palsy. CONCLUSIONS. These data implicate the apolipoprotein E ε4 and ε2 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.