The Relationship Between the Vitamin D Receptor Gene and Anti-155/140 Antibodies in UK Caucasians with Idiopathic Inflammatory Myositis

Purpose: Idiopathic inflammatory myopathy (IIM) is a complex disease and is due to the interaction of environmental and genetic risk factors. A latitudinal gradient exists for IIM, whereby increasing ultraviolet (UV) exposure is associated with the preferential development of dermatomyositis (DM), rather than polymyositis (PM). IIM also displays seasonal variation which may be related to UV exposure. 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. Method: 362 UK Caucasian adult and juvenile onset cases 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; JDM, n=88, females 71%, mean age of disease onset adults 49+/-14 years, juveniles 6+/-3.6 years. SNPs were selected from the following genes: VDR, glutathione S-transferase pi 1, melanocortin 1 receptor and tyrosinase due to their putative functional role or because they had been used in previous studies. SNPs were removed from further analysis where the assay success rate was