Tags

Type your tag names separated by a space and hit enter

Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians.
J Neurol Sci 2011; 305(1-2):116-20JN

Abstract

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.

Authors+Show Affiliations

Wellcome Trust Centre for Human Genetics and Department of Clinical Neurology, University of Oxford, Oxford, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21440908

Citation

Orton, Sarah-Michelle, et al. "Vitamin D Metabolic Pathway Genes and Risk of Multiple Sclerosis in Canadians." Journal of the Neurological Sciences, vol. 305, no. 1-2, 2011, pp. 116-20.
Orton SM, Ramagopalan SV, Para AE, et al. Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. J Neurol Sci. 2011;305(1-2):116-20.
Orton, S. M., Ramagopalan, S. V., Para, A. E., Lincoln, M. R., Handunnetthi, L., Chao, M. J., ... Ebers, G. C. (2011). Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. Journal of the Neurological Sciences, 305(1-2), pp. 116-20. doi:10.1016/j.jns.2011.02.032.
Orton SM, et al. Vitamin D Metabolic Pathway Genes and Risk of Multiple Sclerosis in Canadians. J Neurol Sci. 2011 Jun 15;305(1-2):116-20. PubMed PMID: 21440908.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D metabolic pathway genes and risk of multiple sclerosis in Canadians. AU - Orton,Sarah-Michelle, AU - Ramagopalan,Sreeram V, AU - Para,Andrea E, AU - Lincoln,Mathew R, AU - Handunnetthi,Lahiru, AU - Chao,Michael J, AU - Morahan,Julia, AU - Morrison,Katie M, AU - Sadovnick,A Dessa, AU - Ebers,George C, Y1 - 2011/03/26/ PY - 2010/08/23/received PY - 2011/02/17/revised PY - 2011/02/28/accepted PY - 2011/3/29/entrez PY - 2011/3/29/pubmed PY - 2012/4/4/medline SP - 116 EP - 20 JF - Journal of the neurological sciences JO - J. Neurol. Sci. VL - 305 IS - 1-2 N2 - 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. SN - 1878-5883 UR - https://www.unboundmedicine.com/medline/citation/21440908/Vitamin_D_metabolic_pathway_genes_and_risk_of_multiple_sclerosis_in_Canadians_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-510X(11)00108-0 DB - PRIME DP - Unbound Medicine ER -