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Genetic Links to Rare Liver Disease Found
Date:6/10/2009

nalyzed blood samples from patients with primary biliary cirrhosis as well as samples from people who did not have the condition.

In the first phase of the study, researchers did a genomewide analysis, comparing the genotypes of 536 patients with primary biliary cirrhosis with 1,536 people who did not have the disease. In the next phase, researchers conducted genetic mapping to confirm the initial results and to identify genetic variations closely associated with primary biliary cirrhosis.

Siminovitch's group found variants of two genes, interleukin 12A (IL12A) and interleukin 12RB2 (IL12RB2), that were strongly linked with the disease. In addition, they confirmed that the human leukocyte antigen (HLA) area of the genome is associated with primary biliary cirrhosis, a link that had been identified before.

Dr. Scott L. Friedman, chief of the division of liver diseases at Mount Sinai School of Medicine in New York City and president of the American Association for the Study of Liver Diseases, said the discoveries are an important step in understanding this disease, but the interaction between genes and environmental triggers is complicated.

"I don't think this is going to translate to a significant change in therapy in the near term," Friedman said. "But it opens the door to scientific investigation of other therapies."

Dr. Nathan M. Bass, medical director of the liver transplant service for adults at University of California, San Francisco, noted the study was the first of its kind in primary biliary cirrhosis "that appears to shed light on the mechanism of this uncommon, but puzzling, disease."

"Primary biliary cirrhosis is a distressing condition that mainly affects women, and which has eluded our understanding despite many years of research, although a disorder in immune regulation has been suspected for some time," Bass said.

"The findings of this study suggest that the key problem may rest wit
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