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SCIENTIFIC PUBLICATIONS BY ALR FUNDED RESEARCHERS

How Genes Determine SLE Phenotype and Outcome

Silverman, Earl, MD

The Hospital for Sick Children

Systemic lupus erythematous is a multi-organ system disease that likely results from a complex interaction of genes and the environment. The disease can begin at almost any age, from infants as young as 1 year to individuals in their eighties and even nineties. However, the younger the patient, the more severe the disease tends to be, although its course differs in every patient. Thus, different genes may be involved based on when someone develops lupus. 

So far, however, genetic studies have found one common set of genes in both children and adults with SLE. No one has looked to see whether the amount of genetic changes in children with lupus differ from those in adults with the disease.

In addition, the varying manifestations of lupus from patient to patient suggest that interactions between lupus-related genes and non-lupus-related genes my influence the course of the disease. 

This grant will be used to try and answer both questions: are there differences in the number of genetic mutations between children and adults with lupus? And are there interactions between organ-specific genes and lupus-related genes that help explain the different manifestations of the disease? If so, are these interactions similar in adults and children? 

To investigate these questions, Dr. Silverman and his team will assess 1,000 to 2,000 adults and a similar number of children with lupus in this international study. 

What this study means for people with lupus: Identifying children who have a high genetic risk for lupus will add to our understanding of the pathogenesis of the disease and help explain why it occurs throughout the lifespan. In addition, examining the role of non-lupus genes in patients with lupus will provide important information about how other genes influence the outcome of lupus. Better understanding both of these processes will enable researchers to identify new targets for therapy and to better target existing therapies for children and adults with lupus.


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