Arthritis Foundation Grant Funding a Study on Interplay Between Genes and Environment in Juvenile Arthritis

Arthritis Foundation Grant Funding a Study on Interplay Between Genes and Environment in Juvenile Arthritis
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A University at Buffalo pediatric professor has received a $731,000 Arthritis Foundation grant to study the interplay between genes and the environment that leads to immune dysfunction in patients with juvenile arthritis.

“Our preliminary studies present the hope that we can finally understand” the gene-environment connection in juvenile idiopathic arthritis, Dr. James Jarvis said in a press release. He works at the State University of New York’s Buffalo campus, which is also called the University at Buffalo.

Scientists have long considered juvenile arthritis, or JIA, an autoimmune disease — that is, one in which the immune system attacks healthy cells instead of invaders. But Jarvis believes it may develop due to genetic and epigenetic changes that reduce certain cells’ ability to regulate gene expression. Expression is the process by which a gene creates a functional product like a protein.

Epigenetic changes refer to modifications in gene expression that are unrelated to changes in the genetic code. Epigenetics can influence how cells respond to the environment.

Specifically, epigenetic changes determine “what genes a cell will turn on or turn off in response to environmental cues,” said Jarvis, whose grant is for two years.

“Our field has been dominated by a single hypothesis for JIA pathogenesis [the way a disease develops] for 30 years,” he said. “However, as the field of functional genomics becomes increasingly wedded to the field of therapeutics, our work carries the promise of completely new approaches to therapy based on a completely different paradigm of pathogenesis.”

 

Jarvis’ team plans to recruit 30 children with JIA and 30 healthy children for the study, which will be titled “Interplay Between Genetics and Epigenetics in Polyarticular JIA.”

The goal is to investigate the epigenetic changes of  CD4+ T cells, a type of immune cell that plays a role in JIA.

“We plan to build a multidimensional genomic map that surveys the functional epigenome, examines underlying genetic variation and examines the effects of genetic and epigenetic variation on gene expression,” Jarvis said.

By determining the epigenetic landscape of CD4+ T cells in patients with JIA, researchers will be able to identify epigenetic changes, how they are associated with the expression of different genes, and how both factors converge to promote the development of JIA.

“This project addresses a question that parents always ask, which I never thought we’d begin to answer in my lifetime: ‘What causes JIA?,'” Jarvis said. “This study won’t provide the whole answer, but it will go a long way toward taking us there.”

The project has three aims. First, researchers plan to examine DNA methylation patterns in patients’ CD4+ T cells. DNA methylation is an epigenetic modification. It refers to adding a methyl group to DNA.

Researchers want to correlate DNA methylation levels in CD4+ T cells with gene expression. They will do this by sequencing RNA from the cells. RNA transmits genetic information from DNA so that proteins can be produced.

The next goal is to correlate DNA methylation with what scientists call transposase-accessible chromatin-sequencing, which determines which genes are open, or accessible to be expressed, and which are closed, or inaccessible. This will also allow researchers to link epigenetic changes with gene expression.

Finally, researchers want to do genome sequencing of patients to understand how both the genetic and epigenetic dimensions are affected in the disease.

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