Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals
Brain iron homeostasis is known to be disturbed in multiple sclerosis (MS), yet little is known about the association of common gene variants linked to iron regulation and pathological tissue changes in the brain. In this study, we investigated the association of genetic determinants linked to iron...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-01-01
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| Series: | NeuroImage: Clinical |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213158217302838 |
| _version_ | 1818251590329434112 |
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| author | Jesper Hagemeier Murali Ramanathan Ferdinand Schweser Michael G. Dwyer Fuchun Lin Niels Bergsland Bianca Weinstock-Guttman Robert Zivadinov |
| author_facet | Jesper Hagemeier Murali Ramanathan Ferdinand Schweser Michael G. Dwyer Fuchun Lin Niels Bergsland Bianca Weinstock-Guttman Robert Zivadinov |
| author_sort | Jesper Hagemeier |
| collection | DOAJ |
| description | Brain iron homeostasis is known to be disturbed in multiple sclerosis (MS), yet little is known about the association of common gene variants linked to iron regulation and pathological tissue changes in the brain. In this study, we investigated the association of genetic determinants linked to iron regulation with deep gray matter (GM) magnetic susceptibility in both healthy controls (HC) and MS patients. Four hundred (400) patients with MS and 150 age- and sex-matched HCs were enrolled and obtained 3T MRI examination. Three (3) single nucleotide polymorphisms (SNPs) associated with iron regulation were genotyped: two SNPs in the human hereditary hemochromatosis protein gene HFE: rs1800562 (C282Y mutation) and rs1799945 (H63D mutation), as well as the rs1049296 SNP in the transferrin gene (C2 mutation). The effects of disease and genetic status were studied using quantitative susceptibility mapping (QSM) voxel-based analysis (VBA) and region-of-interest (ROI) analysis of the deep GM. The general linear model framework was used to compare groups. Analyses were corrected for age and sex, and adjusted for false discovery rate. We found moderate increases in susceptibility in the right putamen of participants with the C282Y (+6.1ppb) and H63D (+6.9ppb) gene variants vs. non-carriers, as well as a decrease in thalamic susceptibility of progressive MS patients with the C282Y mutation (left: −5.3ppb, right: −6.7ppb, p<0.05). Female MS patients had lower susceptibility in the caudate (−6.0ppb) and putamen (left: −3.9ppb, right: −4.6ppb) than men, but only when they had a wild-type allele (p<0.05). Iron-gene linked increases in putamen susceptibility (in HC and relapsing remitting MS) and decreases in thalamus susceptibility (in progressive MS), coupled with apparent sex interactions, indicate that brain iron in healthy and disease states may be influenced by genetic factors. Keywords: Iron related genes, Quantitative susceptibility mapping, QSM, Iron, Multiple sclerosis |
| first_indexed | 2024-12-12T16:10:42Z |
| format | Article |
| id | doaj.art-d24d8251e8e84d728e0da655839a0955 |
| institution | Directory Open Access Journal |
| issn | 2213-1582 |
| language | English |
| last_indexed | 2024-12-12T16:10:42Z |
| publishDate | 2018-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | NeuroImage: Clinical |
| spelling | doaj.art-d24d8251e8e84d728e0da655839a09552022-12-22T00:19:12ZengElsevierNeuroImage: Clinical2213-15822018-01-0117530540Iron-related gene variants and brain iron in multiple sclerosis and healthy individualsJesper Hagemeier0Murali Ramanathan1Ferdinand Schweser2Michael G. Dwyer3Fuchun Lin4Niels Bergsland5Bianca Weinstock-Guttman6Robert Zivadinov7Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA; Corresponding author at: Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, 100 High St., Buffalo, NY 14203, USA.Department of Pharmaceutical Sciences, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY, USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA; Center for Biomedical Imaging, Clinical and Translational Science Institute, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USAJacobs Multiple Sclerosis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USABuffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USA; Center for Biomedical Imaging, Clinical and Translational Science Institute, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, The State University of New York, Buffalo, NY, USABrain iron homeostasis is known to be disturbed in multiple sclerosis (MS), yet little is known about the association of common gene variants linked to iron regulation and pathological tissue changes in the brain. In this study, we investigated the association of genetic determinants linked to iron regulation with deep gray matter (GM) magnetic susceptibility in both healthy controls (HC) and MS patients. Four hundred (400) patients with MS and 150 age- and sex-matched HCs were enrolled and obtained 3T MRI examination. Three (3) single nucleotide polymorphisms (SNPs) associated with iron regulation were genotyped: two SNPs in the human hereditary hemochromatosis protein gene HFE: rs1800562 (C282Y mutation) and rs1799945 (H63D mutation), as well as the rs1049296 SNP in the transferrin gene (C2 mutation). The effects of disease and genetic status were studied using quantitative susceptibility mapping (QSM) voxel-based analysis (VBA) and region-of-interest (ROI) analysis of the deep GM. The general linear model framework was used to compare groups. Analyses were corrected for age and sex, and adjusted for false discovery rate. We found moderate increases in susceptibility in the right putamen of participants with the C282Y (+6.1ppb) and H63D (+6.9ppb) gene variants vs. non-carriers, as well as a decrease in thalamic susceptibility of progressive MS patients with the C282Y mutation (left: −5.3ppb, right: −6.7ppb, p<0.05). Female MS patients had lower susceptibility in the caudate (−6.0ppb) and putamen (left: −3.9ppb, right: −4.6ppb) than men, but only when they had a wild-type allele (p<0.05). Iron-gene linked increases in putamen susceptibility (in HC and relapsing remitting MS) and decreases in thalamus susceptibility (in progressive MS), coupled with apparent sex interactions, indicate that brain iron in healthy and disease states may be influenced by genetic factors. Keywords: Iron related genes, Quantitative susceptibility mapping, QSM, Iron, Multiple sclerosishttp://www.sciencedirect.com/science/article/pii/S2213158217302838 |
| spellingShingle | Jesper Hagemeier Murali Ramanathan Ferdinand Schweser Michael G. Dwyer Fuchun Lin Niels Bergsland Bianca Weinstock-Guttman Robert Zivadinov Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals NeuroImage: Clinical |
| title | Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals |
| title_full | Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals |
| title_fullStr | Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals |
| title_full_unstemmed | Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals |
| title_short | Iron-related gene variants and brain iron in multiple sclerosis and healthy individuals |
| title_sort | iron related gene variants and brain iron in multiple sclerosis and healthy individuals |
| url | http://www.sciencedirect.com/science/article/pii/S2213158217302838 |
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