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Convergent effects of a functional C3 variant on brain atrophy, demyelination, and cognitive impairment in multiple sclerosis
- Source :
- Multiple Sclerosis Journal. 25:532-540
- Publication Year :
- 2018
- Publisher :
- SAGE Publications, 2018.
-
Abstract
- Background: Complement system activation products are present in areas of neuroinflammation, demyelination, and neurodegeneration in brains of patients with multiple sclerosis (MS). C3 is a central element in the activation of complement cascades. A common coding variant in the C3 gene (rs2230199, C3R102G) affects C3 activity. Objectives: To assess the effects of rs2230199 on MS severity using clinical, cognitive, and imaging measures. Methods: In total, 161 relapse-onset MS patients (Expanded Disability Status Scale (EDSS) ≤ 6) underwent physical assessments, cognitive tests (Paced Auditory Serial Addition Test (PASAT), Symbol Digit Modalities Test (SDMT), and California Verbal Learning Test (CVLT)), and magnetic resonance imaging (MRI). Lesion volumes were quantified semi-automatically. Voxel-wise analyses were performed to assess the effects of rs2230199 genotype on gray matter (GM) atrophy ( n = 155), white matter (WM) fractional anisotropy (FA; n = 105), and WM magnetization transfer ratio (MTR; n = 90). Results: While rs2230199 minor-allele dosage (C3-102G) showed no significant effect on EDSS and Multiple Sclerosis Functional Composite (MSFC), it was associated with worse cognitive performance ( p = 0.02), lower brain parenchymal fraction ( p = 0.003), and higher lesion burden ( p = 0.02). Moreover, voxel-wise analyses showed lower GM volume in subcortical structures and insula, and lower FA and MTR in several WM areas with higher copies of rs2230199 minor allele. Conclusion: C3-rs2230199 affects white and GM damage as well as cognitive impairment in MS patients. Our findings support a causal role for complement system activity in the pathophysiology of MS.
- Subjects :
- Adult
Male
medicine.medical_specialty
Multiple Sclerosis
Paced Auditory Serial Addition Test
Audiology
White matter
03 medical and health sciences
0302 clinical medicine
Atrophy
Fractional anisotropy
Humans
Medicine
Cognitive Dysfunction
030212 general & internal medicine
Gray Matter
Central element
Expanded Disability Status Scale
California Verbal Learning Test
medicine.diagnostic_test
business.industry
Multiple sclerosis
Complement C3
medicine.disease
Magnetic Resonance Imaging
White Matter
Diffusion Tensor Imaging
medicine.anatomical_structure
Neurology
Female
Neurology (clinical)
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14770970 and 13524585
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Multiple Sclerosis Journal
- Accession number :
- edsair.doi.dedup.....16139360769524d7d8dfcbf0f32b24db
- Full Text :
- https://doi.org/10.1177/1352458518760715