Genetic analysis of vitamin D related genes in Canadian multiple sclerosis patients

Steckley, J L; Dyment, D A; Sadovnick, A. Dessa; Risch, Neil; Hayes, Colleen E.; Ebers, G. C.

doi:10.1212/wnl.54.3.729

Cited by 92 publications

(63 citation statements)

References 5 publications

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“…Vitamin D-supplemented MS patients experienced, after a period of 1-2 years, less than half the number of exacerbations expected on the basis of their case histories [35]. In a Japanese MS case-control study, an excessive representation of the b allele for the vitamin D receptor gene (OR 2.45; 95% Cl 1.20-5.00) was found among MS patients compared to controls [36], but no evidence for linkage or association of vitamin D receptor gene or other candidate genes for MS was found in a Canadian population [37].…”

Section: Discussionmentioning

confidence: 95%

Regional Variation in Multiple Sclerosis Prevalence in Australia and Its Association with Ambient Ultraviolet Radiation

et al. 2001

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The aim of this study was to conduct an ecological analysis of the extent to which ultraviolet radiation (UVR) levels might explain the regional variation of multiple sclerosis (MS) in Australia. MS prevalence data for six Australian regions were compared with UVR levels of the largest city in each region, with some other climatic variables and with the melanoma incidence in the same regions. A close association was found between the theoretical MS prevalence predicted from UVR levels and the actual prevalence. Furthermore, the negative correlation between UVR and MS prevalence (r = –0.91, p = 0.01) was higher than the positive correlation observed for UVR and malignant melanoma incidence (r = 0.75, p = 0.15 for males and r = 0.80, p = 0.10 for females). This study demonstrated that the regional variation in MS prevalence in the continent of Australia could be closely predicted by regional UVR levels. It is consistent with the hypothesis that UVR exposure may reduce the risk of MS possibly via T-lymphocyte-mediated immunosuppression. Analytical epidemiology studies are required to investigate this specific hypothesis.

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Section: Discussionmentioning

confidence: 95%

Regional Variation in Multiple Sclerosis Prevalence in Australia and Its Association with Ambient Ultraviolet Radiation

et al. 2001

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“…In another Japanese study, DBP polymorphism showed no differences in distribution between MS patients and non-related healthy individuals (Niino et al, 2002). In a Canadian population, no evidence was found for association or linkage of genes involved in the metabolism and function of vitamin D with MS, including the 1a-OHase gene, the DBP gene, and the VDR gene (Steckley et al, 2000).…”

Section: Ms and Vitamin D-related Genetic Polymorphismmentioning

confidence: 90%

Multiple sclerosis and vitamin D: an update

et al. 2004

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MS is a chronic, immune-mediated inflammatory and neurodegenerative disease of the central nervous system (CNS), with an etiology that is not yet fully understood. The prevalence of MS is highest where environmental supplies of vitamin D are lowest. It is well recognized that the active hormonal form of vitamin D, 1,25-dihydroxyvitamin D (1,25-(OH) 2 D), is a natural immunoregulator with anti-inflammatory action. The mechanism by which vitamin D nutrition is thought to influence MS involves paracrine or autocrine metabolism of 25OHD by cells expressing the enzyme 1a-OHase in peripheral tissues involved in immune and neural function. Administration of the active metabolite 1,25-(OH) 2 D in mice and rats with experimental allergic encephalomyelitis (EAE, an animal model of MS) not only prevented, but also reduced disease activity. 1,25-(OH) 2 D alters dendritic cell and T-cell function and regulates macrophages in EAE. Interestingly, 1,25-(OH) 2 D is thought to be operating on CNS constituent cells as well. Vitamin D deficiency is caused by insufficient sunlight exposure or low dietary vitamin D 3 intake. Subtle defects in vitamin D metabolism, including genetic polymorphisms related to vitamin D, might possibly be involved as well. Optimal 25OHD serum concentrations, throughout the year, may be beneficial for patients with MS, both to obtain immune-mediated suppression of disease activity, and also to decrease disease-related complications, including increased bone resorption, fractures, and muscle weakness.

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“…Steckely et al 34 found no evidence for linkage or association of VDR [12q14] loci with MS in a Canadian population. Recently, a meta-analysis of VDR polymorphisms and MS showed that ApaI, BsmI, FokI and TaqI VDR polymorphisms are not associated with MS risk.…”

Section: Introductionmentioning

confidence: 99%

Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case–control studies

et al. 2014

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Vitamin D receptor (VDR) polymorphisms have been studied as potential contributors to multiple sclerosis (MS). However, published studies differ with respect to study design and the significance of the effects detected. The aim of this study was to quantify the magnitude of the risk associated with the TaqI, BsmI, ApaI and FokI VDR polymorphisms in MS using a meta-analysis approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search and meta-analysis of the literature. Subgroup analyses were performed to detect potential sources of heterogeneity from the selected study characteristics. The stability of the summary risk was evaluated using sensitivity analyses. The meta-analysis included a total of 3300 cases and 3194 controls from 13 casecontrol studies. There were no significant associations found between TaqI and BsmI polymorphisms and MS risk. The association between the ApaI polymorphism and MS risk was significant in the homozygous and codominant models (P50.013 and P50.031, respectively), suggesting that the AA ApaI genotype might be a significant MS risk factor. Publication year and age significantly affected the association between TaqI polymorphisms and MS (P50.014 and P50.010, respectively), which indicates a protective effect of the major T allele. The AA ApaI and FF FokI genotypes are significant risk factors for MS. The association between the TaqI polymorphism and MS risk is significantly affected by study characteristics.

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Genetic analysis of vitamin D related genes in Canadian multiple sclerosis patients

Cited by 92 publications

References 5 publications

Regional Variation in Multiple Sclerosis Prevalence in Australia and Its Association with Ambient Ultraviolet Radiation

Regional Variation in Multiple Sclerosis Prevalence in Australia and Its Association with Ambient Ultraviolet Radiation

Multiple sclerosis and vitamin D: an update

Association between vitamin D receptor polymorphisms and multiple sclerosis: systematic review and meta-analysis of case–control studies

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