Vitamin D receptor polymorphisms and HLA-class II genotypes among Lebanese with multiple sclerosis – A pilot study

Multiple studies have provided evidence for an association between reduced sun exposure and increased risk of multiple sclerosis (MS), an association likely to be mediated, at least in part, by the vitamin D hormonal pathway. Herein, we examine whether the vitamin D receptor ( VDR), an integral component of this pathway, influences MS risk in a population-based sample where winter sun exposure in early childhood has been found to be an important determinant of MS risk. Three polymorphisms within the VDR gene were genotyped in 136 MS cases and 235 controls, and associations with MS and past sun exposure were examined by logistic regression. No significant univariate associations between the polymorphisms, rs11574010 ( Cdx-2A > G), rs10735810 ( Fok1T > C), or rs731236 ( Taq1C > T) and MS risk were observed. However, a significant interaction was observed between winter sun exposure during childhood, genotype at rs11574010, and MS risk ( P = 0.012), with the ‘G’ allele conferring an increased risk of MS in the low sun exposure group (≤2 h/day). No significant interactions were observed for either rs10735810 or rs731236, after stratification by sun exposure. These data provide support for the involvement of the VDR gene in determining MS risk, an interaction likely to be dependent on past sun exposure.

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Multiple Sclerosis in French Canadians: Evidence for HLA Class II Susceptibility and Resistance Genes

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100030924 ◽

1990 ◽

Vol 17 (4) ◽

pp. 382-386 ◽

Cited By ~ 8

Author(s):

D.G. Haegert ◽

M. Michaud ◽

G.S. Francis

Keyword(s):

Multiple Sclerosis ◽

Resistance Genes ◽

Rflp Analysis ◽

Class Ii ◽

Hla Class Ii ◽

Extended Haplotype ◽

Allele Specific ◽

Relationship Of ◽

The Relationship ◽

Susceptibility And Resistance

ABSTRACT:HLA class II DRBI, DQB1 and DQA1 gene probes were used to study DNA from unrelated French Canadian multiple sclerosis (MS) patients and controls by restriction fragment length polymorphism (RFLP) analysis. An MS-associated and linked series of allele-specific RFLPs or allogenotypes was identified among this relatively homogeneous ethnic group; the allogenotypes include DRwl5, DQw6 and a DQA1 allogenotype termed DQαlb. An additional allogenotype which cross-hybridizes with DQA1 and is termed DQA2 upper (DQA2U), was shown not only to be part of the MS-associated extended haplotype, but also to be independently associated with MS in DRwl5-negative patients. Conversely a second DQA2 allogenotype, termed DQA2 lower (DQA2L) and a DQB1 allogenotype (DQw7) linked to DQA2L showed negative correlations with MS. It seems likely that the relationship of the HLA class II gene region to MS is complex and that MS susceptibility may reflect interaction between disease susceptibility and resistance genes.

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Association of a Polymorphism Within Intron 8 But Not Exon 9 of the Vitamin D Receptor in Patients With Multiple Sclerosis of Southeastern Iranian Ethnicity

Laboratory Medicine ◽

10.1309/lm8gljhwing18clb ◽

2013 ◽

Vol 44 (3) ◽

pp. 215-219 ◽

Cited By ~ 2

Author(s):

Reza Mosavi ◽

Mohammad Kazemi Arababadi ◽

Gholamhossein Hassanshahi ◽

Hossein Azin ◽

Majid Araste ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Vitamin D Receptor ◽

Exon 9

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Predisposing role of vitamin D receptor (VDR) polymorphisms in the development of multiple sclerosis: A case-control study

Journal of the Neurological Sciences ◽

10.1016/j.jns.2016.05.053 ◽

2016 ◽

Vol 367 ◽

pp. 148-151 ◽

Cited By ~ 16

Author(s):

Rasoul Abdollahzadeh ◽

Mahsa Sobhani Fard ◽

Farideh Rahmani ◽

Kaveh Moloudi ◽

Behrooz Sadeghi kalani ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Vitamin D Receptor ◽

Case Control Study ◽

Case Control ◽

Control Study ◽

Vdr Polymorphisms

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HLA class II alleles in patients with multiple sclerosis in the Biscay province (Basque Country, Spain)

Journal of Neurology ◽

10.1007/s00415-009-5223-2 ◽

2009 ◽

Vol 256 (12) ◽

pp. 1977-1988 ◽

Cited By ~ 17

Author(s):

Oscar Fernández ◽

Alfredo R-Antigüedad ◽

María Jesús Pinto-Medel ◽

Mari Mar Mendibe ◽

Nestor Acosta ◽

...

Keyword(s):

Multiple Sclerosis ◽

Basque Country ◽

Class Ii ◽

Hla Class Ii ◽

Hla Class Ii Alleles

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Molecular network of chromatin immunoprecipitation followed by deep sequencing-based vitamin D receptor target genes

Multiple Sclerosis Journal ◽

10.1177/1352458512471873 ◽

2013 ◽

Vol 19 (8) ◽

pp. 1035-1045 ◽

Cited By ~ 19

Author(s):

Jun-ichi Satoh ◽

Hiroko Tabunoki

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Vitamin D Receptor ◽

Deep Sequencing ◽

Immune Cells ◽

Chromatin Immunoprecipitation ◽

Target Genes ◽

Molecular Network ◽

Genome Wide

Background: Vitamin D is a liposoluble vitamin essential for calcium metabolism. The ligand-bound vitamin D receptor (VDR), heterodimerized with retinoid X receptor, interacts with vitamin D response elements (VDREs) to regulate gene expression. Vitamin D deficiency due to insufficient sunlight exposure confers an increased risk for multiple sclerosis (MS). Objective: To study a protective role of vitamin D in multiple sclerosis (MS), it is important to characterize the global molecular network of VDR target genes (VDRTGs) in immune cells. Methods: We identified genome-wide VDRTGs collectively from two distinct chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) datasets of VDR-binding sites derived from calcitriol-treated human cells of B cell and monocyte origins. We mapped short reads of next generation sequencing (NGS) data on hg19 with Bowtie, detected the peaks with Model-based Analysis of ChIP-Seq (MACS), and identified genomic locations by GenomeJack, a novel genome viewer for NGS platforms. Results: We found 2997 stringent peaks distributed on protein-coding genes, chiefly located in the promoter and the intron on VDRE DR3 sequences. However, the corresponding transcriptome data verified calcitriol-induced upregulation of only a small set of VDRTGs. The molecular network of 1541 calcitriol-responsive VDRTGs showed a significant relationship with leukocyte transendothelial migration, Fcγ receptor-mediated phagocytosis, and transcriptional regulation by VDR, suggesting a pivotal role of genome-wide VDRTGs in immune regulation. Conclusion: These results suggest the working hypothesis that persistent deficiency of vitamin D might perturb the complex network of VDRTGs in immune cells, being responsible for induction of an autoimmune response causative for MS.

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