IN UK CAUCASIAN ADULT AND JUVENILE-ONSET DERMATOMYOSITIS (DM), THE VITAMIN D RECEPTOR GENE (VDR) IS ASSOCIATED WITH POSSESSION OF ANTI-155/140 ANTIBODIES

Background: The aetiology of idiopathic inflammatory myopathies (IIM) is thought due to the interaction of environmental and genetic risk factors. Recent studies show that alleles in the human leukocyte antigen (HLA) region confer strong susceptibility for the development of adult and juvenile onset IIM. Furthermore, a latitudinal gradient appears to exist for IIM, whereby increasing ultraviolet (UV) exposure is associated with the preferential development of (especially anti-Mi-2 positive) dermatomyositis (DM), rather than polymyositis (PM). A further DM-specific antibody, anti-155/140, has recently been described in adult and juvenile DM. VDR and other single nucleotide polymorphisms (SNPs) putatively related to UV susceptibility are associated with other conditions where UV exposure is an aetiological risk factor, including prostate cancer and multiple sclerosis. We hypothesise that such polymorphisms are associated with the development of IIM. Methods: 362 UK Caucasian adult and juvenile onset cases with probable/definite IIM (Bohan & Peter, 1975) were recruited from the UK Adult Onset Myositis Immunogenetic Collaboration and the Juvenile Dermatomyositis (JDM) National Registry and Repository. They were compared to 287 matched Caucasian controls: PM, n=112; DM, n=98; myositis/overlap, n=64; juvenile DM, n=88, females 71%, median age of disease onset adults 49+/-14 years, juveniles 6+/-6.5 years. SNPs were selected from the following genes: VDR, glutathione S-transferase pi 1, melanocortin 1 receptor and tyrosinase. Haplotype tagging SNPs were selected for genotyping using the Hapmap CEU population, (release 20, NCBI B35 assembly) by pairwise tagging, r2 cut-off 0.8 and a minimum allelic frequency of 10%. SNPs were also selected on the basis of having a putative functional role or from investigation in previous studies. SNPs were removed from further analysis where the assay success rate was