Genetic study adds weight to vitamin D role in MS risk
medwireNews: A Mendelian randomisation study supports the theory that low 25-hydroxyvitamin D (25[OH]D) levels could increase people’s multiple sclerosis (MS) risk.
“The importance of these findings may be magnified in high-latitude countries, which have disproportionately higher rates of MS and also higher rates of vitamin D insufficiency”, say Brent Richards (McGill University, Montreal, Quebec, Canada) and study co-authors.
The team’s Mendelian analysis found that, among 14,498 MS cases and 24,091 healthy controls of European descent, each standard deviation decrease in genetically determined 25(OH)D levels was associated with a significant 2.02-fold increase in the risk of having MS.
Using data from 33,996 individuals of European descent from 15 cohorts, the researchers identified four single nucleotide polymorphisms (SNPs) that were significantly associated with reduced 25(OH)D levels. All the SNPs were located near genes that had strong associations with vitamin D synthesis, transport or metabolism: GC, DHCR7, CYP2R1 and CYP24A1. The team assessed the effect of these SNPs on the odds of having MS, adjusted for the magnitude of change each SNP induces in 25(OH)D levels.
The association between genetically determined 25(OH)D levels and MS risk persisted in sensitivity analyses accounting for possible pleiotropy and a variant with a likely non-European origin, Richards et al report in PLoS Medicine.
Mendelian analysis uses the random assignment of SNPs to avoid the problems of confounding encountered in observational studies. Thus, it is able to assess the effects of people’s lifetime exposure to a variable – in this case low vitamin D levels.
For this reason, the researchers stress that randomised trials of vitamin D supplementation may need to be very long-term to demonstrate an effect. They suggest that a “reasonable first step” would be to test supplementation in patients with clinically isolated syndrome.
In a press statement, Danny Altmann, Professor of Immunology at Imperial College London, UK, who was not involved in the study, cautioned that in many other conditions studied, “the notion that all will be well if we simply give patients a large dose of vitamin D supplements has proved too simple.”
He said: “While it may be too much to expect therapeutic vitamin D to treat or reverse ongoing MS, this paper will add to the weight of argument for routine vitamin D supplementation of foodstuffs as a broad, preventative, public health measure.”
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