The effect of NF-𝜿B risk variant on TMSX-PET-evaluated astroglial activation in MS patients

Abstract

Objective To investigate the effect of the NF-κB risk allele, rs7665090-G, on PET-evaluated astrocytic activation and lesion pathology in multiple sclerosis.

Methods Thirty-four patients with MS (6 with the protective phenotype rs7665090-AA, 15 with the heterozygous phenotype rs7665090-GA, and 13 with the homozygous risk allele rs7665090-GG) and nineteen healthy controls underwent conventional brain MRI and [11C]-TMSX-PET imaging. Mean DVRs were calculated from deep NAWM, T1 3-6 mm rim, thalamus, and cortical GM. Disability was evaluated based on Expanded Disability Status Scale (EDSS) scores. Spearman correlations were used to assess the relationships between DVRs and MRI lesion loads.

Results Disabilities did not differ between the three subgroups with the varying genotypes. Among the patients carrying the risk genotype, deep NAWM (ρ=0.69, p=0.009) and T1 3-6mm rim (ρ=0.65, p=0.017) DVRs correlated positively with the T1 lesion load. The protective genotype (rs7665090-AA) was associated with higher thalamus DVR compared to the risk genotype (rs7665090-GG) (p=0.016).

Conclusions The findings of this study suggest that the NF-κB risk variant, rs7665090-G, may contribute to astrocyte-driven chronic lesion associated pathology. Genotyping for this risk variant could be included in the progression risk assessment of MS patients.