Researcher Abigail Wexner Research Institute, Nationwide Children’s Hospital, United States
Introduction/Rationale: Juvenile dermatomyositis (JDM) and Systemic Lupus Erythematosus (SLE) are systemic autoimmune diseases characterized by production of autoantibodies against cellular and nuclear antigens and complement-mediated tissue injuries. Common clinical presentations of JDM and cSLE include photosensitive rashes on the skin, although the patterns of rash are different. We seek to determine the genetic features of these two diseases.
Methods: Data from whole exomes sequencing of 51 patients with JDM and 43 patients with cSLE revealed two nonsynonymous variants, S192Y and R402Q in the tyrosinase gene (TYR), which encodes a key enzyme in melanin biosynthesis and skin pigmentation. We developed restriction fragment length polymorphisms (RFLP) of PCR amplified genomic DNA fragments using Hpy188I digest or HpyAV digest to identify the S192Y and R402Q variations, respectively.
Results: The S192Y variant has significantly higher frequency in JDM than controls (41% vs 25%, p=0.0003), while R402Q has higher frequency in cSLE than controls (32.6% vs 17.6%, p=0.0006). Intriguingly, another protein engaged in the melanin synthesis pathway, melanocortin-1 receptor MC1R, has non-synonymous variant for R160W. FauI RFLP was developed to detect this R160W polymorphism in MC1R. Close to 21.6% JDM patients have a homozygous or heterozygous variant of R160W in MC1R (p=0.001).
Conclusion: Overall, 88% of patients with JDM or cSLE have a variant in S192Y or R402Q of TYR, or R160W of MC1R. Further experiments are in progress to manipulate the expression and functional activities of TYR and MC1R.
