Study reveals new genetic link to scleroderma

Posted on Tuesday, June 22nd, 2010

An international research consortium including scientists from the Medical School has identified a new genetic link to the systemic form of scleroderma.

In the May print issue of Nature Genetics, scientists report they found a new region of the human genome associated with increased systemic scleroderma susceptibility.

“With our latest discovery, we are probably a quarter of the way to finding the genes and pathways responsible for systemic scleroderma,” said Dr. Maureen Mayes, one of the study’s senior authors and a professor of rheumatology. “Once most of the important genes are found, we will be able to focus on developing interventions to block their activity.”

Researchers believe a thorough understanding of the genetic nature of the disease is crucial to developing a cure to systemic scleroderma, which is a profoundly disabling autoimmune disease that affects about 100,000 people in the United States.

In the study, scientists used a genetic research technique called a genome-wide association study that allows researchers to detect genetic variations associated with a particular disease. It was the first large application of this technique to systemic scleroderma, she said.

A genetic comparison of 2,296 people with systemic scleroderma to 5,171 without the disease led scientists to a region of the genome known as CD247. “This region contains a gene that is central to immunity, which makes this very exciting,” Mayes said.

Findings were confirmed during a second test involving 2,753 people with systemic scleroderma and 4,569 without systemic scleroderma. Participants were from the United States, Spain, Germany, and The Netherlands.

Dr. Frank Arnett, one of the senior authors and professor of internal medicine, said research shows that scleroderma shares many susceptibility genes with lupus and other autoimmune diseases. One day, researchers may be able to more specifically target the causative pathways in each of these conditions, said Arnett, holder of the Elizabeth Bidgood Chair in Rheumatology and the Linda K. Finger Chair in Autoimmune and Connective Tissue Diseases.

The study also confirmed the link between systemic scleroderma and three other previously discovered areas of the genome – MHC, IRF5 and STAT4, Mayes said.

Building on this research, Mayes said scientists now plan to conduct a second study involving patients recruited from 10 scleroderma centers in the United States and Canada. “This will allow us to examine the findings more closely,” she said.

Peggy Brown, who is the vice president of the Texas Bluebonnet Chapter of the Scleroderma Foundation, is heartened by the research. “If they can figure out what causes it, they can find a cure,” Brown said.

Also contributing to the study from the Division of Rheumatology were Drs. Sandeep Agarwal, assistant professor; Shervin Assassi, assistant professor; Pravitt Gourh, internal medicine resident; and Filemon Tan, associate professor.

Dr. Olga Gorlova, associate professor in the Department of Epidemiology at The University of Texas M. D. Anderson Cancer Center, also was one of the senior authors.

The study, which is titled “Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus,” received support from the National Institutes of Health.

- Rob Cahill, Office of Institutional Advancement, Media Relations

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