Introduction: The prevalence of multiple sclerosis (MS) shows a latitude gradient which may be related to exposure to ultraviolet radiation (UVR). The effects of UVR may be mediated through 1,25-dihydroxycholecalciferol which exerts its effects via the vitamin D receptor. We hypothesised that polymorphisms in the vitamin D receptor gene (VDR) are associated with risk and severity of multiple sclerosis. We also hypothesised that MS cases may be clustered in space as a reflection of shared aetiological exposures. Methods: We examined g. 1229A>G, g. 3436C>G, g. 3944G>A, g. 20965C>T, g. 30056C>T, g. 30875T>C, g. 48200C>T, and g. 65013C>T single nucleotide polymorphisms in patients with multiple sclerosis (Poser criteria) and controls using pyrosequencing technology. Disability was assessed with the expanded disability status scale (EDSS) and was dichotomised into mild to moderate (EDSS <6) and severe (EDSS>6) disability. Genotypes and haplotypes at the 8 sites were analysed for association with disability (in patients with disease duration >10 years) and risk (in the case and control groups) using logistic regression with corrections for age, gender and disease duration. Results: U30875 genotype was significantly associated with less severe disability (EDSS<6) (odds ratio=0.37,95% CI=0.20-0.70, p=0.048). Genotype combinations including TT3087w5 ere also associated with less severe disability. Non-significant associations with MS risk (after correction formultiple comparisons) were found for AA 3944a nd CT3 0875 . Haplotype G3436_ G3 944w as associated with reduced risk of MS whereas A3944C 2096h5a plotype was risk conferring. Conclusions: We demonstrate associations between VDR polymorphisms and MS severity and risk. These preliminary results will need confirmation in independent cohorts.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:518335 |
| Date | January 2009 |
| Creators | Mamutse, Godwin |
| Publisher | Keele University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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