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Modulating effects of WT 1 on interferon‐ β ‐vitamin D association in MS
Author(s) -
Lin R.,
Taylor B. V.,
Charlesworth J.,
Mei I.,
Blizzard L.,
Stewart N.,
Ponsonby A.L.,
Dwyer T.,
Pittas F.,
Simpson S.
Publication year - 2015
Publication title -
acta neurologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.967
H-Index - 95
eISSN - 1600-0404
pISSN - 0001-6314
DOI - 10.1111/ane.12315
Subject(s) - single nucleotide polymorphism , vitamin d and neurology , medicine , interferon , genotype , calcitriol receptor , cohort , gastroenterology , gene , endocrinology , oncology , biology , immunology , genetics
Objective To investigate whether those genes involved in the vitamin D pathway modulate the relationship between 25‐hydroxyvitamin D (25( OH )D) and IFN ‐ β , 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 patients with 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 SNP s (rs10767935 and rs5030244) in WT 1 significantly modified the IFN ‐ β ‐25( OH )D association after adjustment (P interaction = 0.001, 0.0002; P adj = 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 SNP s modified the interaction between IFN ‐ β and 25( OH )D in predicting relapse. Conclusions We have demonstrated that two‐independent SNP s (rs10767935 and rs5030244) in WT 1 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 WT 1 variants may play a role in altering the effects of IFN ‐ β on vitamin D in MS .