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- W1562636992 abstract "Objective: To investigate whether those genes involved in vitamin D pathway modulate the demonstrated relationship between 25-hydroxyvitamin D ((25(OH)D) and IFN-β treatment, the relationship between IFN-β and sun in predicting 25(OH)D, and the interaction between IFN-β and 25(OH)D in modulating relapse risk in people with MS.Methods: We conducted a prospective cohort study of 169 participants with MS and genotype data from 2002 to 2005. Gene-IFN-β and gene-IFN-β-sun interactions on 25(OH)D were evaluated by multilevel mixed-effects linear regression. Gene-IFN-β interactions on 25(OH)D in modulating in relapse risk were assessed using survival analysis. Experiment-wide significance threshold was adjusted by the effective number of independent marker loci (MeffLi) for each gene.Results: Two intronic genotyped SNPs (rs10767935 and rs5030244) in the gene WT1 significantly modified the relationship between IFN-β and 25(OH)D even after adjustment for covariates and multiple comparisons for MeffLi in MS patients (pinteraction=0.001, 0.0002; padj=0.003, 0.006, respectively) and in RRMS subgroup (pinteraction =0.0003, 0.0004; padj =0.0009, 0.0012, respectively). Notable trends were found for these two SNPs on the relationship between sun exposure and IFN-β in predicting 25(OH)D levels, and on the relationship between 25(OH)D and IFN-β influencing relapse risk, though these did not reach statistical significance.Conclusions: We have demonstrated for the first time that two SNPs (rs10767935 and rs5030244) in WT1 significantly modified the previously demonstrated association between IFN-β treatment and 25(OH)D in the patients with MS and RRMS, and showed evidence of modulating the sun-IFN-β-25(OH)D association and the 25(OH)D-IFN-β-relapse association. These findings indicate that WT1 may play an important role in the altering therapeutic effects of IFN-β. Disclosure: Dr. Lin has nothing to disclose. Dr. Simpson, Jr. has nothing to disclose. Dr. Charlesworth has nothing to disclose. Dr. van der Mei has nothing to disclose. Dr. Blizzard has nothing to disclose. Dr. Stewart has nothing to disclose." @default.
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- W1562636992 date "2014-04-08" @default.
- W1562636992 modified "2023-09-23" @default.
- W1562636992 title "Modulating Effects Of WT1 On The Relationship Between Interferon-β and Vitamin D Levels In The Patients With Multiple Sclerosis (P6.146)" @default.
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