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The Relationship Between the Vitamin D Receptor Gene and Anti-155/140 Antibodies in UK Caucasians with Idiopathic Inflammatory Myositis
Kapoor, S.R., Chinoy, H., Wedderburn, L.R., Oddis, C.V., McHugh, N.J., Ollier, W.E., Cooper, R.G
In: Arthritis Rheum : American College of Rheumatology; Pennsylvania. 2009. p. 60:S300.
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Abstract
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 <90% and sample success <80%. Results were thus available for 38 SNPs. Circulating antibodies (anti-Jo-1, PL-7, PL-12, EJ, OJ, KS, Mi-2, SRP, U1/U3-RNP, Ku, PM-Scl, 155/140) were detected using immunoprecipitation. Results: All 38 SNPs conformed to Hardy Weinberg equilibrium in controls. No SNP was associated in the overall or traditional clinical sub-groups. Anti-155/140 antibodies were detected in 29 patients, all of whom had DM. Possession of the A allele in a VDR haplotype tagging SNP (rs2254210) was associated with possession of anti-155/140 antibodies (51%), compared to both controls (33%) (odds ratio 2.1, 95% confidence interval 1.2-3.8, p=0.006) and anti-155/140 antibody negative cases (36%) (1.9, 1.1-3.4, p=0.01). Associations for this SNP were observed independently in the juvenile and adult 155/140 (+) sub-groups. No other significant associations were observed in any of the remaining serologically-defined sub-groups. Conclusion: The rs2254210 polymorphism in the VDR gene is a possible risk factor in juvenile and adult anti-155/140 positive DM patients.