Association of CYP2R1 rs10766197 with MS risk and disease progression

Scazzone, Concetta; Agnello, Luisa; Ragonese, Paolo; Sasso, Bruna Lo; Bellia, Chiara; Bivona, Giulia; Schillaci, Rosaria; Salemi, Giuseppe; Ciaccio, Marcello

doi:10.1002/jnr.24133

Cited by 41 publications

(35 citation statements)

References 36 publications

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“…Le Mokry et al (2015) identified SNPs associated with 25(OH)D level from SUNLIGHT, the largest ( n = 33,996) genome-wide association study to date for vitamin D. Four SNPs were genome-wide significant for 25(OH)D levels, and all four SNPs lay in, or near, genes strongly implicated in separate mechanisms influencing 25(OH)D. The authors found out that the count of the 25(OH)D-decreasing alleles across these four SNPs was strongly associated with a lower 25(OH)D level. Other recent perspectives [95] confirmed the research by Ahn et al [93]; it seems that there are strong links between the 25(OH)D levels and the genotyping of CYP2R1- and NAD-synthetase (NADSYN1-SNPs) in MS patients. The analysis revealed lower 25(OH)D concentrations in MS patients and an association of rs10766197 CYP2R1 SNP with MS risk.…”

Section: Vitamin D Deficiency and Multiple Sclerosis: Role In The supporting

confidence: 60%

“…Several genome-wide association studies (GWAS) and gene-candidate studies have investigated the influence of the specific genetic polymorphisms of vitamin D metabolites on the 25(OH)D levels, and their susceptibility to MS; one study found [92] an association between the short variant of the VDR protein (F allele) and a genetic predisposition to lower 25(OH)D levels, but not to a higher risk of MS; in a GWAS of 4501 European patients [93], single-nucleotide polymorphisms (SNPs) of the gene encoding components of the vitamin D binding protein were associated with 25(OH)D concentrations, or with the genes involved in vitamin D synthesis or activation; moreover, a genetically lowered 25(OH)D level was strongly associated with increased MS risk and progression in two studies [94,95]. …”

Section: Vitamin D Deficiency and Multiple Sclerosis: Role In The mentioning

confidence: 99%

“…According to other authors, as a goal, the general aim is 25(OH)D levels between 40 and 60 ng/mL, and most patients should take a dose that arises from 2000 to 5000 IU/day vitamin D3 [123]. Many studies have been conducted to show the potential relationships between genome-wide association studies (GWAS) and gene-candidate studies, in order to find out the specific genetic polymorphisms of the vitamin D metabolites on the 25(OH)D levels, and their susceptibility to MS and to vitamin D supplementation efficacy in MS [92,93,94,95]. Moreover, the Human Leukocyte Antigen (HLA) haplotype might influence epistasis, trans and cis effects, and parent-of-origin effects, as well as the Epstein Barr Virus (EBV) and vitamin D effects on the course of MS [124].…”

Section: Vitamin D Deficiency and Multiple Sclerosis: Role In The mentioning

confidence: 99%

“…The analysis revealed lower 25(OH)D concentrations in MS patients and an association of rs10766197 CYP2R1 SNP with MS risk. After stratifying the MS patients according to gender, the authors [95] found that the minor allele A of rs10766197 had a higher frequency in men in comparison with the women affected by MS. Additionally, the presence of allele A in men was associated with disease progression, assessed by EDSS and Multiple Sclerosis Severity Score (MSSS) scores [96]. The results are not univocal at all; a recent study focussed on VDR polymorphisms (Fok-I, Bsm-I, Taq-I, and Apa-I) that were genotyped by a polymerase chain reaction (PCR), followed by the restriction fragment length polymorphism (RFLP) analyses in both groups, and the serum 25(OH) D levels were determined in the MS patients by high-performance liquid chromatography (HPLC).…”

Section: Vitamin D Deficiency and Multiple Sclerosis: Role In The mentioning

confidence: 99%

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Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

Moretti

Morelli

Caruso

2018

IJMS

130

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It is widely known that vitamin D receptors have been found in neurons and glial cells, and their highest expression is in the hippocampus, hypothalamus, thalamus and subcortical grey nuclei, and substantia nigra. Vitamin D helps the regulation of neurotrophin, neural differentiation, and maturation, through the control operation of growing factors synthesis (i.e., neural growth factor [NGF] and glial cell line-derived growth factor (GDNF), the trafficking of the septohippocampal pathway, and the control of the synthesis process of different neuromodulators (such as acetylcholine [Ach], dopamine [DA], and gamma-aminobutyric [GABA]). Based on these assumptions, we have written this review to summarize the potential role of vitamin D in neurological pathologies. This work could be titanic and the results might have been very fuzzy and even incoherent had we not conjectured to taper our first intentions and devoted our interests towards three mainstreams, demyelinating pathologies, vascular syndromes, and neurodegeneration. As a result of the lack of useful therapeutic options, apart from the disease-modifying strategies, the role of different risk factors should be investigated in neurology, as their correction may lead to the improvement of the cerebral conditions. We have explored the relationships between the gene-environmental influence and long-term vitamin D deficiency, as a risk factor for the development of different types of neurological disorders, along with the role and the rationale of therapeutic trials with vitamin D implementation.

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Section: Vitamin D Deficiency and Multiple Sclerosis: Role In The supporting

confidence: 60%

Section: Vitamin D Deficiency and Multiple Sclerosis: Role In The mentioning

confidence: 99%

Section: Vitamin D Deficiency and Multiple Sclerosis: Role In The mentioning

confidence: 99%

Section: Vitamin D Deficiency and Multiple Sclerosis: Role In The mentioning

confidence: 99%

See 2 more Smart Citations

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

Moretti

Morelli

Caruso

2018

IJMS

130

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“…In a study of over 7000 individuals with MS, a genetic burden score was not associated with disability . Other smaller studies have reported associations of several genetic variants and progression of disability but have not yet been replicated …”

Section: Cause Versus Course – Are the Risk Factors Different?mentioning

confidence: 94%

Environmental and genetic risk factors for MS: an integrated review

Waubant

Lucas

Mowry

et al. 2019

Ann Clin Transl Neurol

217

184

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Recent findings have provided a molecular basis for the combined contributions of multifaceted risk factors for the onset of multiple sclerosis (MS). MS appears to start as a chronic dysregulation of immune homeostasis resulting from complex interactions between genetic predispositions, infectious exposures, and factors that lead to pro‐inflammatory states, including smoking, obesity, and low sun exposure. This is supported by the discovery of gene–environment (GxE) interactions and epigenetic alterations triggered by environmental exposures in individuals with particular genetic make‐ups. It is notable that several of these pro‐inflammatory factors have not emerged as strong prognostic indicators. Biological processes at play during the relapsing phase of the disease may result from initial inflammatory‐mediated injury, while risk factors for the later phase of MS, which is weighted toward neurodegeneration, are not yet well defined. This integrated review of current evidence guides recommendations for clinical practice and highlights research gaps.

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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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Association of CYP2R1 rs10766197 with MS risk and disease progression

Abstract: The findings of our study open new perspectives for a role of CYP2R1 in both risk and progression of MS, with sex-related differences.

Cited by 41 publications

References 36 publications

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

Vitamin D in Neurological Diseases: A Rationale for a Pathogenic Impact

Environmental and genetic risk factors for MS: an integrated review

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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