SCN1A rs3812718 polymorphism modulates structural and functional brain networks in TLE: A multimodal imaging-genomics...

Area of Science:

• Neuroscience
• Genetics
• Medical Imaging

Background:

• Temporal lobe epilepsy (TLE) is a common neurological disorder with complex genetic and structural underpinnings.
• The SCN1A gene plays a crucial role in neuronal excitability and has been implicated in various epilepsy syndromes.

Purpose of the Study:

• To investigate the impact of the SCN1A rs3812718 polymorphism on gray matter volume (GMV) and resting-state functional network topology in TLE patients.
• To identify potential genetic-neuroimaging biomarkers for TLE.

Main Methods:

• Genotyping and MRI (3D-T1, rs-fMRI) were performed on 60 TLE patients and 28 healthy controls (HCs).
• Voxel-based morphometry assessed GMV, and graph theory analyzed functional network topology.
• 2x2 ANCOVA was used to test for main effects of genotype, disease status, and their interaction.

Main Results:

• The AA/AG genotype was more frequent in TLE patients compared to HCs.
• A significant genotype main effect revealed reduced GMV in temporal regions and hippocampus for AA/AG carriers.
• A significant genotype-by-disease interaction showed the most extensive GMV reductions in TLE patients with the AA/AG genotype, particularly in the inferior temporal gyrus, fusiform gyri, and hippocampus.

Conclusions:

• The SCN1A rs3812718 AA/AG genotype is a TLE risk factor.
• This genotype is associated with structural brain alterations (GMV) and functional network changes in TLE.
• These genetic-neuroimaging signatures hold promise as biomarkers for TLE precision medicine.