OBJECTIVE: To compare vitamin D level-associated single-nucleotide polymorphisms (SNPs) in GC and CYP2R1, multiple sclerosis (MS) risk SNPs in CYP27B1, CYP24A1, and HLA-DRB1*1501, and adolescent exposure to environmental risk factors for hypovitaminosis D, with MS age at onset.

METHODS: This cross-sectional study included 1161 Danish patients with MS; lifestyle questionnaires and blood samples for genotyping were collected from all participants from 2009 to 2012. Information on age at onset was obtained from the Danish MS Treatment Registry. Written informed consent was obtained from all study participants, and the study was approved by the local ethics committee.

RESULTS: Younger age at onset was significantly associated with low exposure to summer sun in adolescence, higher body mass index at 20 years of age, and the HLA-DRB1*1501 risk allele in both univariate analyses and in a multivariable regression analysis. No association was found between age at onset and any of the other SNPs or vitamin D-associated environmental factors.

CONCLUSION: We demonstrate an independent effect by HLA-DRB1*1501, adolescent summer sun habits, and body mass index at the age of 20 on age at onset of MS.