No evidence for the rare CYP27B1 as susceptibility locus

Epub: Barizzone et al. No evidence for a role of rare CYP27B1 functional variations in multiple sclerosis. Ann Neurol. 2012 Dec 13. doi: 10.1002/ana.23834.

Background: Association studies have implicated common variants in the 12q14.1 region containing CYP27B1 in multiple sclerosis (MS). Rare CYP27B1 mutations cause autosomal recessive vitamin D-dependent rickets type 1, and it has recently been reported that heterozygous CYP27B1 mutations are associated with increased MS susceptibility and lower active vitamin D levels. 

Methods and results: By sequencing CYP27B1 in 134 multiplex families and genotyping the most common variant R389H in 2,608 MS patients and 1,987 controls from Italy and Belgium (a total of 4,729 individuals), we were unable to replicate these observations.

Conclusions: These results provide evidence against a major role for CYP27B1 mutations in MS

This study supports recent study from Cambridge, but  does not support the work by Ram and the Oxford Group. Maybe Ram will post a comment

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  • Yes another negative study suggesting that there may be no association with variants at this locus and MS risk. Explanations as before exist, especially population differences. Interestingly (to me) 4 new variants were identified in the Italian MS patients that have never been reported before despite looking at thousands of people, however the authors of this study chose to ignore this.

    • The previously unreported mutations are interesting. 2 of them are in untranslated regions (but this doesn't mean that they aren't important!), the other 3 in intronic regions (which are removed from the final gene, but again, that doesn't mean they aren't important). It would be interesting to study those families in more detail…

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