Gene sequences regulating the production of apoE and cerebral palsy of variable severity

Abstract

Background: The apoE protein is the most important lipid transporter in the brain and has also been shown to have several regulatory functions in the central nervous system. The production of apoE is regulated by a number of genes and increases under certain conditions such as cerebral injury in adults.

Aims: Our aim was to study whether variations in genes regulating the expression of the APOE gene were associated with severity of cerebral palsy (CP).

Methods: Children enrolled in the Cerebral Palsy Register of Norway (CPRN) were invited to participate in this cross-sectional study; 281 of the invited 703 children (40%) returned swabs with buccal cells collected by parents. Six genetic variations thought to affect the production of apoE were genotyped and correlated with clinical data recorded in the CPRN.

Results: Compared with children carrying the GG allele, children with genotype GT or TT in a specific genetic variation (rs59007384 located in the nearby TOMM40 gene) had excess risk for worse fine motor function (Odds ratio (OR): 1.82; 95% Confidence interval (CI): 1.10-2.99; p = 0.019) and epilepsy (OR: 2.32; CI: 1.17-4.61; p = 0.016). There was no association between severity of CP and any of the other five genetic variations analyzed.

Conclusion: Our findings suggest that genetic variations in one of the sequences regulating the expression of APOE, may be associated with worse clinical outcome in children with cerebral palsy.

Keywords: APOE; APOE regulator genes; Severity of CP.