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Published on: January 11, 2016
Apolipoprotein E and functional motor severity in cerebral palsy
James A Blackman1, Matthew J Gurka, Yongde Bao
1Department of Pediatrics, University of Virginia, Charlottesville, VA, USA.
Insights
The APOE ε4 allele may protect young children from severe cerebral palsy (CP). This genetic factor showed a trend towards reduced CP severity, especially with perinatal brain injury.
Area of Science:
- Neuroscience
- Genetics
- Developmental Pediatrics
Background:
- Cerebral palsy (CP) arises from non-progressive brain disturbances in early development.
- The APOE ε4 allele's role in brain injury outcomes differs between adults and young children.
- Previous research suggests APOE ε4 may be protective in very young populations.
Purpose of the Study:
- To investigate the hypothesis that the APOE ε4 allele is associated with reduced cerebral palsy severity.
- To explore the potential protective role of APOE ε4 in pediatric brain injury.
Main Methods:
- Genotyping of the APOE gene in 158 individuals with CP and their parents.
- Analysis of the association between APOE ε4 allele presence/number and CP severity.
- Family-based analysis using Transmission Disequilibrium Test (TDT) to assess genetic effects.
Main Results:
- 30% of CP subjects carried at least one APOE ε4 allele.
- A trend suggested individuals with an ε4 allele had lower CP severity (p=0.11).
- Higher ε4 allele count correlated with lower CP severity (p=0.12); perinatal brain injury significantly predicted lower severity (p<0.01).
Conclusions:
- The APOE ε4 allele may confer protection against severe cerebral palsy in children.
- Findings suggest a contrasting role of APOE ε4 in pediatric versus adult brain injury outcomes.
- Further research is warranted to confirm APOE ε4's protective effect in fetal/neonatal brain injury.
Abstract:
Cerebral palsy is attributed to non-progressive disturbances in the developing fetal or infant brain. The APOE ε4 allele has been associated with poor outcome after brain injury in adults but may be protective among very young children. We conducted this study to explore the hypothesis that the APOE ε4 is associated with lowered severity of cerebral palsy. 158 individuals with CP and their parents were genotyped for APOE. Mean age was 9.1 years; 54% were males. 61% were preterm at birth; 34% less than 30 weeks gestation. 30% of the CP subjects had at least one ε4 allele. There was a trend towards significance for subjects with at least one ε4 allele assigned to the low severity group (p = 0.11). The greater number of ε4 alleles, the more likely an individual was in the low severity CP group (p = 0.12). Individuals with brain injury in the perinatal period were almost 5 times more likely to be in the low severity group (p < 0.01). Family analysis via the TDT supported a protective effect of APOE ε4. Further study is needed to confirm that, in contrast to adults, the APOE ε4 allele appears to confer protection and/or facilitate recovery after brain injury in the fetus or newborn, particularly when that injury occurs around term.
