Modulating effects of WT1 on interferon-β-vitamin D association in MS
Methods:Prospective cohort study of 169 participants with MS and genotype data followed 2002–2005. Gene-IFN-β and gene-IFN-β-sun interactions predicting 25(OH)D evaluated by multilevel mixed-effects linear regression. Gene-IFN-β interactions with 25(OH)D in modulating in relapse risk assessed using survival analysis.
Results:The cohort was 71.6% female and of mean age 47.8. Two-independent intronic genotyped SNPs (rs10767935 and rs5030244) in WT1 significantly modified the IFN-β-25(OH)D association after adjustment (Pinteraction = 0.001, 0.0002; Padj = 0.003, 0.006, respectively). There was a marked difference in the interaction between self-reported sun exposure and IFN-β in predicting 25(OH)D by level of rs10767935, although this did not reach statistical significance. No SNPs modified the interaction between IFN-β and 25(OH)D in predicting relapse.
Conclusions:We have demonstrated that two-independent SNPs (rs10767935 and rs5030244) in WT1 modified the IFN-β-25(OH)D association in patients with MS. Some evidence was shown for a difference in the sun-IFN-β-25(OH)D association by level of rs10767935. These findings indicate that WT1 variants may play a role in altering the effects of IFN-β on vitamin D in MS.
Publication titleActa Neurologica Scandinavica
Department/SchoolMenzies Institute for Medical Research
Place of publication35 Norre Sogade, Po Box 2148, Copenhagen, Denmark, Dk-1016
Rights statementCopyright 2014 Wiley-Blackwell