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Apolipoprotein e and cerebral palsy severity

JA BLACKMAN MD MPH, MJ GURKA PHD, Y BAO PHD,
B DRAGULEV PHD, MJ ROMNESS MD

University of Virginia, Charlottesville, VA, USA

Background/Objectives: Cerebral Palsy (CP) is a disturbance of movement and posture resulting from injury to the developing brain. The Apolipoprotein E gene codes for three isoforms: apo E2, E3, and E4. The APO E e4allele has been associated with poor outcome after brain injury in adults but may be protective among very young children. Conversely, the e2 allele is protective in adults, but may pose risk in infants. We investigated the relationship between the APO e4allele and severity of motor impairment in CP.

Design: A cross-sectional study of APO E genotypes and gross motor function classification among individuals with CP.

Participants and Setting: 153 individuals with CP at the University of Virginia or its satellite clinic. Mean age was 9.1 years; 54% were males, 61% were preterm at birth; 35% less than 30 weeks gestation.

Materials/Methods: Genomic DNA was extracted from buccal swabs for APO E genotyping by Taqman Fluorescent Resonance Energy Transfer (FRED) assays on each participant. Functional motor severity was assessed by the Gross Motor Function Classification System (GMFCS), on a scale of 1-5, grouped as levels 1-2 (low severity) and 3-5 (high severity). A chi-square analysis was performed to assess the association between the presence of the APO E e4 allele and severity. Logistic regression was applied to adjust for other risk factors, such as timing of brain injury, gestational age, and type of CP.

Results: 31% of subjects had at least one e4 allele. There was a trend towards significance for subjects with at least one e4 allele assigned to the low severity group (p=.11) . e4 was significantly associated with low severity when adjusted for the effect of timing of injury. Infants with brain injury in the perinatal period were 4.3 times more likely to be in the low severity group (p=.01).

Conclusions/Significance: In contrast to adults, the APO E e4 allele appears to confer protection and/or facilitate recovery after brain injury in the fetus or newborn, particularly when that injury occurs around term. This finding has important implications for future clinical trials that mimic the salutary effects of APO E. It is important to know whether the E4 isoform is helpful or harmful in the immature brain.

 
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