Presence of Apolipoprotein E ϵ4 Allele in Cerebral Palsy

Abstract

The apolipoprotein E gene, which is located on chromosome 19, has three alleles (epsilon2, epsilon3, and epsilon4). Several recent publications associate the presence of the apolipoprotein E epsilon4 allele with the occurrence of neurologic diseases, and consider it a risk factor for the development of central nervous system affections. A group of 40 patients with cerebral palsy was studied and compared to a control group of 40 subjects, and higher occurrence of the allele epsilon4 in the group of subjects with cerebral palsy was observed. A significantly higher risk of developing cerebral palsy was demonstrated among those subjects with the apolipoprotein E epsilon4 allele.

Candidate Genes and Risk for CP: A Population-Based Study

“…Commercial Applied Biosystems Taqman SNP probes (Foster City, California) were used to genotype single nucleotide polymorphisms (SNPs) using 0.5ng of genomic DNA (Table 1). We genotyped the following SNP’s that have been previously associated with CP: tumor necrosis factor-α (TNF-α) -308 (rs1800629) (8), interleukin-8 (IL-8) -251 (rs4073) (6), lymphotoxin 60 (rs1041981) (6, 11), endothelial nitric oxide synthase (eNOS) -922 (rs1800779) (11), inducible nitric oxide synthase (iNOS) -231 (rs1137933) (6), endothelial protein C receptor (EPCR) 219 (rs867186) (6), mannose binding lectin (MBL) 54 (rs1800450) and 52 (rs5030737) (8), factor V Leiden (FVL) 506 (rs6025) (10), methyltetrahydrofolate reductase (MTHFR) 1298 (rs1801131) and 667 (rs1801133) (10), prothrombin 20210 (rs1799963) (10), platelet activator inhibitor (PAI-1) 11053 (rs7242) (11), and apolipoprotein E (apo E) E2 and E4 alleles (rs429358 and rs7412) (15, 16, 18). The IL-6 -174 polymorphism was previously studied in this population (5), and therefore was not included in the current study.…”

“…The ε4 allele of the apolipoprotein E (apoE) gene has also been associated with CP in more than one population (15, 16), though not all studies have supported this finding (17, 18). Few genetic studies of CP have been conducted in the US, and the majority of findings have yet to be corroborated in an independent cohort.…”

Apolipoprotein E genotype and outcome in infants with hypoxic–ischemic encephalopathy

“…Two recent reports (24, 25) of subjects with CP have not found the strengths of association found in the two earlier reports of association between CP and APOE genotype (13, 14). Wu et al reported results of association studies between candidate gene SNPs and cerebral palsy from a diverse, general population of 334,333 newborn infants from the Kaiser Permanente Health System, inclusive of healthy and sick infants.…”

“…Previous case – control studies of pediatric populations reporting association between APOE genotypes and CP, a common outcome after HIE, did not target assessment of only infants with neonatal hypoxic-ischemic injury (13, 14). Our results demonstrate no association between APOE genotype and moderate or severe disability, or specifically with CP, in this more restrictive injury phenotype, and no modification from use of hypothermia.…”

“…Previous case-control studies in children with cerebral palsy (CP), a morbidity that occasionally follows HIE, have demonstrated associations between the APOE e4 allele and increased severity of CP, microcephaly, and seizures (13, 14). These studies included both term and preterm infants with various forms of CP.…”