OBJECTIVE: To determine the motor-behavioral and neural correlates of putative functional common variants in the @entity1372 -channel @entity8603 encoding gene ( @entity8603 ) in vivo in @entity1 with @entity15 ( @entity15 ). METHODS: We recruited 161 @entity1 with relapsing-onset @entity15 and 94 demographically comparable healthy @entity1 . All @entity1 with @entity15 underwent structural MRI and clinical examinations (Expanded Disability Status Scale [EDSS] and @entity15 Functional Composite [MSFC]). Whole-brain voxel-wise and cerebellar volumetry were performed to assess differences in regional brain volumes between genotype groups. Resting-state fMRI was acquired from 62 @entity1 with @entity15 to evaluate differences in cerebellar functional connectivity. All @entity1 were genotyped for 4 potentially functional @entity8603 polymorphisms. RESULTS: Two @entity8603 polymorphisms in high linkage disequilibrium (r(2) = 0.95) showed significant association with MSFC performance in @entity1 with @entity15 ( @entity52407 : p = 6.2 * 10(-4); @entity70041 : p = 0.0025). @entity1 with @entity15 with @entity52407 (AA) genotype performed significantly worse than @entity52407 (G) carriers in MSFC (p = 1.8 * 10(-4)) and all of its subscores. This association was independent of EDSS and @entity76 . Although the genotype groups showed no difference in regional brain volumes, @entity52407 (AA) carriers demonstrated significantly diminished cerebellar functional connectivity with the thalami and midbrain. No significant @entity8603 -genotype effect was observed on MSFC performance in healthy @entity1 . CONCLUSIONS: Our data suggest that @entity8603 variation substantially influences functional status, including prominent effects on motor coordination in @entity1 with @entity15 . These findings were supported by the effects of this variant on a neural system important for motor coordination, namely cerebello-thalamic circuitry. Overall, our findings add to the emerging evidence that suggests that @entity1372 channel @entity8603 could serve as a target for future drug-based interventions to treat @entity76 in @entity15 .

Channelopathy-related @entity8603 gene variants predict @entity76 in XXXX .

@entity1 :: ('9606', 'Species') :: ['participants', 'Patients', 'patients'] @entity52407 :: ('rs6795970', 'SNP') :: ['rs6795970'] @entity8603 :: ('6336', 'Gene') :: ['SCN10A', 'NaV1.8'] @entity1372 :: ('MESH:D012964', 'Chemical') :: ['sodium'] @entity70041 :: ('rs6801957', 'SNP') :: ['rs6801957'] @entity76 :: ('MESH:D002526', 'Disease') :: ['cerebellar atrophy', 'cerebellar dysfunction'] @entity15 :: ('MESH:D009103', 'Disease') :: ['MS', 'Multiple Sclerosis', 'multiple sclerosis']
@entity15 :: (MESH:D009103,Disease) :: ['multiple sclerosis']
