Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians

Orton, Sarah-Michelle; Ramagopalan, Sreeram; Para, Andrea E.; Lincoln, Matthew R.; Handunnetthi, Lahiru; Chao, Michael J.; Morahan, Julia M.; Morrison, Katie; Sadovnick, A. Dessa; Ebers, George C.

doi:10.1016/j.jns.2011.02.032

Cited by 65 publications

(57 citation statements)

References 47 publications

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“…It has been indicated that MS has a higher frequency in women (8-10, 32, 44, 45). The effects of patient sex on MS prevalence have also been confirmed in previous studies (9,18,32,38,(44)(45)(46).…”

Section: Discussionsupporting

confidence: 74%

“…In addition, heredity plays a prominent role in the occurrence of the illness in populations (44,(52)(53)(54). MS is initiated by environmental factors in persons with genetic-risk profiles (4), and it is the result of an interaction of genetic background and environmental factors (5,9,45,(55)(56)(57).…”

Section: Discussionmentioning

confidence: 99%

“…It is reported that multiple environmental factors (sunlight/vitamin D3 and metabolism) in conjunction with genetic risk contribute to MS promotion in the molecular mechanism (5,9,(56)(57)(58). Genetics influence the regulation of seasonal vitamin D concentrations in MS twins (10).…”

Section: Discussionmentioning

confidence: 99%

“…The separate areas are recognized as inflammation, demyelination, axonal loss, and gliosis (plaques) in the CNS (4). Different factors, such as autoimmune mechanisms, genetic background (5-7), and environmental factors (8)(9)(10)(11), have been known to play roles in the occurrence of MS even though the main etiology of this disease is unidentified.…”

Section: Introductionmentioning

confidence: 99%

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Frequency of Multiple Sclerosis (MS) Among Relatives of MS Patients in Hamadan Society, Iran

Mazdeh

Khazaei

Hashemi-Firouzi

et al. 2016

Avicenna J Neuro Psycho Physiology

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Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system with unknown causes. In the last decade, the prevalence of MS in Iran has increased. Objectives: This study evaluated the frequency of familial MS among patients in the Hamadan society for MS. Patients and Methods: This cross-sectional study was performed on 1202 MS patients in Farshchian hospital, Hamadan, in 2013. All patients were diagnosed with definite MS. A questionnaire was used to gather information; demographic characteristics, medical history, signs and symptoms at onset, course of disease, relatives with MS, and degree and type of relationship were recorded.

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Section: Discussionsupporting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Frequency of Multiple Sclerosis (MS) Among Relatives of MS Patients in Hamadan Society, Iran

Mazdeh

Khazaei

Hashemi-Firouzi

et al. 2016

Avicenna J Neuro Psycho Physiology

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“…The genetic involvement of CYP27B1 in MS risk was also found in another GWAS considering a specific pathway in which eight genes within a module of 13 genes influenced by vitamin D were associated with MS [ANZgene and the Australia and New Zealand Multiple Sclerosis Genetics Consortium, 2009] and is now confirmed thanks to several other types of genetic research methods used to study patients with MS with vitamin D-dependent rickets [Torkildsen et al 2008], with rare variants or with single nucleotide polymorphisms [Sundqvist et al 2010;Simon et al 2011]. However, it should be mentioned that no association was found between genes involved in vitamin D metabolism and MS risk in two other studies [Orton et al 2011a;Smolders et al 2011c], but these studies were performed with a much smaller sample than the one used by Sawcer and colleagues [Sawcer et al 2011]. Furthermore, the genes encoding CYP27B1 and CYP24A1 could be epigenetically regulated [Kim et al 2009;Novakovic et al 2009], which may influence the vitamin D serum level and MS risk [Burrell et al 2011].…”

Section: Genetic Risk Factors For Multiple Sclerosis Possibly Involvimentioning

confidence: 99%

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Pierrot‐Deseilligny

Souberbielle

2013

Ther Adv Neurol Disord

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Abstract:The contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis (MS) is reviewed. Among the multiple recently discovered actions of vitamin D, an immunomodulatory role has been documented in experimental autoimmune encephalomyelitis and in humans. This action in the peripheral immune system is currently the main known mechanism through which vitamin D might influence MS, but other types of actions could be involved within the central nervous system. Furthermore, vitamin D insufficiency is widespread in temperate countries and in patients with MS at the earliest stages of the disease, suggesting that the deleterious effects related to vitamin D insufficiency may be exerted in these patients. In fact, many genetic and environmental risk factors appear to interact and contribute to MS. In genetics, several human leukocyte antigen (HLA) alleles (more particularly HLA-DRB1*1501) could favour the disease whereas some others could be protective. Some of the genes involved in vitamin D metabolism (e.g. CYP27B1) also play a significant role. Furthermore, three environmental risk factors have been identified: past Epstein-Barr virus infection, vitamin D insufficiency and cigarette smoking. Interactions between genetic and environmental risk or protective factors may occur during the mother's pregnancy and could continue during childhood and adolescence and until the disease is triggered in adulthood, therefore possibly modulating the MS risk throughout the first decades of life. Furthermore, some clinical findings already strongly suggest that vitamin D status influences the relapse rate and radiological lesions in patients with MS, although the results of adequately powered randomized clinical trials using vitamin D supplementation have not yet been reported. While awaiting these incontrovertible results, which might be long in coming, patients with MS who are currently in vitamin D insufficiency should be supplemented, at least for their general health status, using moderate doses of the vitamin.

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Exonic variants of genes related to the vitamin D signaling pathway in the families of familial multiple sclerosis using whole‐exome next generation sequencing

et al. 2019

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Introduction Vitamin D (VD) deficiency has been associated with multiple sclerosis (MS) and other autoimmune diseases (AIDs). However, the effect of the genetics of VD on the risk of MS is subject to debate. This study focuses on genes linked to the VD signaling pathway in families with MS. The evaluation of gene variants in all the members of families could contribute to an additional knowledge on the information obtained from case‐control studies that use nonrelated healthy people. Material and Methods We studied 94 individuals from 15 families including at least two patients with MS. We performed whole‐exome next generation sequencing on all individuals and analyzed variants of the DHCR7, CYP2R1, CYP3A4, CYP27A1, GC, CYP27B1, LRP2, CUBN, DAB2, FCGR, RXR, VDR, CYP24A1, and PDIA3 genes. We also studied PTH, FGF23, METTL1, METTL21B, and the role of the linkage disequilibrium block on the long arm of chromosome 12, through analysis of the CDK4, TSFM, AGAP2, and AVIL genes. We compared patients with MS, other AIDs and unaffected members from different family types. Results The study described the variants in the VD signaling pathway that appear in families with at least two patients with MS. Some infrequent variants were detected in these families, but no significant difference was observed between patients with MS and/or other AIDs and unaffected family members in the frequency of these variants. Variants previously associated with MS in the literature were not observed in these families or were distributed similarly in patients and unaffected family members. Conclusion The study of genes involved in the VD signaling pathway in families that include more than one patient with MS did not identify any variants that could explain the presence of the disease, suggesting that VD metabolism could probably play a role in MS more as an environmental factor rather than as a genetic factor. Our study also supports the analysis of cases and unaffected individuals within families in order to determine the influence of genetic factors.

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Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians

Cited by 65 publications

References 47 publications

Frequency of Multiple Sclerosis (MS) Among Relatives of MS Patients in Hamadan Society, Iran

Frequency of Multiple Sclerosis (MS) Among Relatives of MS Patients in Hamadan Society, Iran

Contribution of vitamin D insufficiency to the pathogenesis of multiple sclerosis

Exonic variants of genes related to the vitamin D signaling pathway in the families of familial multiple sclerosis using whole‐exome next generation sequencing

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