Convergent effects of a functional C3 variant on brain atrophy, demyelination, and cognitive impairment in multiple sclerosis
| Autor: | Ali Shakouri Rad, Mohammad Ali Sahraian, Rozita Doosti, Amir Pejman Hashemi Taheri, Mahsa Owji, Masih Falahatian, Tina Roostaei, Abdorreza Naser Moghadasi, Esmaeil Mohamadi, Aria Nazeri, Nina Javadian, Rahil Mashhadi, Shokufeh Sadaghiani, Arash Nazeri, Aristotle N. Voineskos, Amirreza Azimi |
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| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | Multiple Sclerosis Journal. 25:532-540 |
| ISSN: | 1477-0970 1352-4585 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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