The association between APOE gene polymorphisms and the risk, characteristics, and prognosis of epilepsy: A systematic review and meta-analysis

Objective

Epilepsy is one of the most common neurological diseases. Current evidence suggests that the apolipoprotein E (APOE) gene may be related to epilepsy. The purpose was to explore whether the APOE gene is associated with the risk, characteristics, and prognosis of epilepsy.

Methods

The study was a systematic review and meta-analysis. We searched WANFANG, VIP, CNKI, Embase, CENTRAL, and Medline for relevant studies published in English and Chinese inception up to December 27, 2023. Studies containing both APOE genotypes or at least one type of APOE allele and epilepsy were included.

Results

A total of 46 studies were included. Fourteen studies reported APOE genotypes and epilepsy risk (2539 patients and 2847 controls). The meta-analyses showed that the APOE 4 was higher in epilepsy (OR [95 % CI] = 1.32 [1.07, 1.62], I² = 30 %), the APOE 2 was lower in epilepsy (OR [95 % CI] = 0.73 [0.62, 0.87], I² = 0 %), and the APOE 3 didn’t differ between epilepsy and controls (OR [95 % CI] = 1.01 [0.86, 1.19], I² = 29 %). Our findings highlight that the risk of epilepsy is different depending on the subtype, with the APOE gene being more associated with temporal lobe epilepsy, drug-refractory epilepsy, and late-onset epilepsy. Patients with the ɛ4 allele have an earlier onset, worse cognition, and are more likely to have a history of febrile convulsion. No association between the ɛ4 allele and psychiatric symptoms and seizure-free after surgery.

Interpretation

These findings will help inform the provision of epilepsy services, including clinical management an important option for epilepsy patients with cognitive impairment, temporal lobe epilepsy, late-onset epilepsy, and drug-refractory epilepsy. However, whether APOE gene testing should be used as a routine test in people with epilepsy remains to be determined.