Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians.
BACKGROUND: Multiple sclerosis (MS) is determined by interactions between genes and environment and the influence of vitamin D adequacy has been proposed. Previous studies have shown that serum 25-hydroxyvitamin D (25(OH)D) levels are genetically influenced. Polymorphisms in vitamin D pathway genes...
| Asıl Yazarlar: | , , , , , , , , , |
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| Materyal Türü: | Journal article |
| Dil: | English |
| Baskı/Yayın Bilgisi: |
2011
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| _version_ | 1826264808377286656 |
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| author | Orton, S Ramagopalan, S Para, A Lincoln, MR Handunnetthi, L Chao, M Morahan, J Morrison, K Sadovnick, A Ebers, G |
| author_facet | Orton, S Ramagopalan, S Para, A Lincoln, MR Handunnetthi, L Chao, M Morahan, J Morrison, K Sadovnick, A Ebers, G |
| author_sort | Orton, S |
| collection | OXFORD |
| description | BACKGROUND: Multiple sclerosis (MS) is determined by interactions between genes and environment and the influence of vitamin D adequacy has been proposed. Previous studies have shown that serum 25-hydroxyvitamin D (25(OH)D) levels are genetically influenced. Polymorphisms in vitamin D pathway genes are candidates for association with MS susceptibility. METHODS: MS patients (n=1364) and their unaffected first-degree relatives (n=1661) were ascertained through the Canadian Collaborative study. Seventy-one SNPs, across four genes [vitamin D receptor (VDR), 1-alpha-hydroxylase (CYP27B1) enzyme, vitamin D binding protein (DBP), 24-hydroxylase (CYP24)], were genotyped and tested for association with MS susceptibility using TDT in PLINK. Secondary analyses included stratification for HLA-DRB1*15 and parent of origin transmission effects. RESULTS: We found no significant association of vitamin D pathway genes with MS susceptibility after correction for multiple comparisons. However, the VDR Fok1 variant (rs2228570), selected for previously positive associations with MS susceptibility and 25(OH)D levels in MS patients showed marginally distorted transmission in DRB15-negative patients (p=0.03). There was no evidence for differential maternal versus paternal allele transmission. CONCLUSIONS: The findings fail to directly connect vitamin D metabolism genes to MS susceptibility, despite a large sample size and comprehensive gene coverage. |
| first_indexed | 2024-03-06T20:13:48Z |
| format | Journal article |
| id | oxford-uuid:2b75a2b3-b11a-4dc6-ac02-fa6f47877674 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:13:48Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:2b75a2b3-b11a-4dc6-ac02-fa6f478776742022-03-26T12:31:05ZVitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:2b75a2b3-b11a-4dc6-ac02-fa6f47877674EnglishSymplectic Elements at Oxford2011Orton, SRamagopalan, SPara, ALincoln, MRHandunnetthi, LChao, MMorahan, JMorrison, KSadovnick, AEbers, G BACKGROUND: Multiple sclerosis (MS) is determined by interactions between genes and environment and the influence of vitamin D adequacy has been proposed. Previous studies have shown that serum 25-hydroxyvitamin D (25(OH)D) levels are genetically influenced. Polymorphisms in vitamin D pathway genes are candidates for association with MS susceptibility. METHODS: MS patients (n=1364) and their unaffected first-degree relatives (n=1661) were ascertained through the Canadian Collaborative study. Seventy-one SNPs, across four genes [vitamin D receptor (VDR), 1-alpha-hydroxylase (CYP27B1) enzyme, vitamin D binding protein (DBP), 24-hydroxylase (CYP24)], were genotyped and tested for association with MS susceptibility using TDT in PLINK. Secondary analyses included stratification for HLA-DRB1*15 and parent of origin transmission effects. RESULTS: We found no significant association of vitamin D pathway genes with MS susceptibility after correction for multiple comparisons. However, the VDR Fok1 variant (rs2228570), selected for previously positive associations with MS susceptibility and 25(OH)D levels in MS patients showed marginally distorted transmission in DRB15-negative patients (p=0.03). There was no evidence for differential maternal versus paternal allele transmission. CONCLUSIONS: The findings fail to directly connect vitamin D metabolism genes to MS susceptibility, despite a large sample size and comprehensive gene coverage. |
| spellingShingle | Orton, S Ramagopalan, S Para, A Lincoln, MR Handunnetthi, L Chao, M Morahan, J Morrison, K Sadovnick, A Ebers, G Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. |
| title | Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. |
| title_full | Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. |
| title_fullStr | Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. |
| title_full_unstemmed | Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. |
| title_short | Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. |
| title_sort | vitamin d metabolic pathway genes and risk of multiple sclerosis in canadians |
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