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Mayo researchers help discover genetic cause for primary biliary cirrhosis
Date:5/27/2009

mary biliary cirrhosis has been well-established by previous studies. "Indeed, mothers, sisters and daughters in the same family have a significantly higher tendency to develop the disease compared with the general population," says Dr. Lazaridis.

To learn more about the cause of the illness, researchers designed a three-phase study to identify genetic markers associated with the disease. In phase one, researchers conducted a genome-wide association analysis, comparing the genotypes of 536 patients with primary biliary cirrhosis to those of 1,536 people who did not have the disease. Researchers looked at more than 300,000 single-nucleotide polymorphisms (SNPs), the most common genetic variations, among the approximately 11 million known to be present in the human genome.

"There were significant differences between the patients with primary biliary cirrhosis and the control group," says Dr. Lazaridis. As a result, researchers narrowed their focus to 16 SNPs significantly linked to primary biliary cirrhosis.

In phases two and three, researchers conducted "replication" and "fine-mapping" studies to confirm the initial results and to further detail the genetic variations most closely linked to primary biliary cirrhosis.

Researchers discovered that variants of two genes, interleukin 12A (IL12A) and interleukin 12RB2 (IL12RB2), were strongly associated with primary biliary cirrhosis. These two genes constitute a pathway of the immune system. Potential therapeutic manipulation of this pathway provides new possibilities for more effective treatments of these patients, says Dr. Lazaridis.

Researchers also confirmed that the human leukocyte antigen (HLA) region of the genome is linked to primary biliary cirrhosis, an association which had been identified in previous research. "Although both the HLA region and the IL12 pathway are equally involved with susceptibility to primary biliary cirrhosis, HLA is very complicated to dissec
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Contact: Amy Tieder
newsbureau@mayo.edu
507-284-5005
Mayo Clinic
Source:Eurekalert

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