Apolipoprotein E isoforms and susceptibility to genetic generalized epilepsies

Abstract

Background: Apolipoprotein E (ApoE) is the main lipoprotein secreted in brain. It has a critical immunomodulatory function, influences neurotransmission and it is involved in repairing damaged neurons. ApoE e4 is an isoform of ApoE with altered function, and was previously associated with early onset epilepsy and refractoriness, both in animal models and in patients with focal epilepsies. There is a limited knowledge on ApoE’s role in Genetic Generalized Epilepsies (GGE).

Aim: To determine if ApoE isoforms are risk factors for GGE development.

Methods: A group of 337 GGE patients (193 F, 144 M, 33.6 ± 14.2 years) was compared with a group of 342 healthy individuals in a case-control genetic association study. ApoE genotyping was performed using PCR-RFLP.

Results: The genotypic frequency of ApoE e3/e2 was lower in GGE patients relative to controls (6.5% in GGE vs. 11.7% in controls, p = 0.019, OR (95% CI) = 0.53 (0.305–0.905). No associations with other clinical data such as photosensitivity or age at disease onset were observed.

Conclusion: Our results show that ApoE e3/e2 genotype may be a protective factor for GGE development. There is evidence that this genotype could be neuroprotective, preventing oxidative damage and promoting neuronal survival. Although replication studies are warranted, our data suggest that ApoE isoforms have a role in epileptogenic mechanisms regardless of the specific epileptic manifestations.

Keywords:

• Epilepsy
• genetics
• ApoE
• JME
• GGE

Acknowledgments

The funders had no role in study design, data collection and analysis or preparation of the manuscript. The authors acknowledge the nurses from the epilepsy outpatient clinic from collaboration in sample collection and Ms. Maria Rebelo for technical assistance. The greatest acknowledgement is to the patients and their families, for their essential collaboration.

Disclosure statement

The authors have nothing to disclose.

Additional information

Funding

This research was partially funded by a BICE Tecnifar Grant