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

OBJECTIVE

To investigate the impact of the SCN1A rs3812718 polymorphism on gray matter volume (GMV) and resting-state functional network topology in temporal lobe epilepsy (TLE) patients.

METHODS

60 TLE patients and 28 healthy controls (HCs) underwent genotyping and MRI (3D-T1, rs-fMRI). Participants were grouped by genotype (AA/AGvs.GG) and disease status (TLEvs.HC). Voxel-based morphometry assessed GMV; graph theory analyzed functional network topology. 2x2 ANCOVA tested genotype and disease main effects and their interaction.

RESULTS

AA/AG genotype frequency was higher in (TLE vs.HCs). GMV: Significant genotype main effect (AA/AGvs.GG): reduced GMV in right temporal regions/hippocampus/left SMG; increased in left MTG/right precuneus. Significant disease main effect (TLEvs.HC): widespread GMV reductions, especially in mesiotemporal/neocortical areas. Significant genotype-by-disease interaction: TLE patients with AA/AG genotype showed the most extensive GMV reductions (bilateral ITG, fusiform gyri, right hippocampus/precuneus/occipital, left caudate/rectus).

FUNCTIONAL NETWORKS: Significant disease main effect: reduced degree centrality in left dorsolateral prefrontal cortex (SFGdor/MFG) in TLEvs.HC. No significant interaction effects on global/nodal topology.

CORRELATIONS: In AA/AG TLE patients, left MTG GMV negatively correlated with epilepsy duration.

CONCLUSION

The SCN1A rs3812718AA/AG genotype is a TLE risk factor. It independently and interactively (with disease status) is associated with structural brain alterations (GMV) in TLE and is linked to disease-related functional network changes (DC) in cognitive regions. These genetic-neuroimaging signatures offer potential biomarkers for TLE precision medicine.