No evidence for a role of rare CYP27B1 functional variations in multiple sclerosis


Address correspondence to Dr D'Alfonso, Department of Health Sciences, University of Eastern Piedmont, Via Solaroli 17, 28100 Novara, Italy. E-mail: or Dr Goris, Laboratory for Neuroimmunology, Herestraat 49 bus 1022, 3000 Leuven, Belgium. E-mail:


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. 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. These results provide evidence against a major role for CYP27B1 mutations in MS. ANN NEUROL 2013;73:433–437