Study finds links between genetic mutations and lupus

A new research has found that a gene,iscovered by scientists at Wake Forest University School of Medicine, is linked to lupus and related autoimmune diseases.

The finding is the latest in a series of exposures that elucidate the dysfunctions in human cells that cause the diseases.

"This research is a huge leap toward understanding the cause of lupus and related autoimmune diseases. There had been few clues before now," said Fred Perrino, Ph.D., a co-author on the paper and a professor of biochemistry at Wake Forest.

Perrino, who discovered the gene in 1998, said he assumed it was caught up in human disease, but it took a group of researchers from around the world collaborating to solve the puzzle.

"We've known that lupus was a complex disease, but now we have a specific protein and a particular cellular process that appears to be one of the causes. We're connecting the dots to understand the biology of what's going on with the disease," said Perrino.

Lead author Min Ae Lee-Kirsch, M.D., from the Technische Universitt Dresden in Dresden, Germany, and colleagues report finding variations of the TREX1 gene discovered by Perrino in patients with systemic lupus erythematosus. The study involved 417 lupus patients from the United Kingdom and Germany. Mutations were found in nine patients with lupus and were absent in 1,712 people without lupus.

"Our data identify a stronger risk for developing lupus in patients that carry variants of the gene," said Lee-Kirsch.

The diseases are all autoimmuine diseases, implying that the body makes antibodies against itself. In lupus, these antibodies lead to pain and inflammation in various parts of the body, including the skin, joints, heart, lungs, blood, kidneys and brain. The disease is characterized by pain, heat, redness, swelling and loss of function.

Perrino began studying the protein made by the gene more than 14 years ago.

"We basically cracked open cells to locate the protein and find the gene. In the 14 years since, we've learned a lot about the protein and how it functions," said Perrino.

The gene produces a protein, also known as TREX1, whose job is to "disassemble" or "unravel" DNA, the filament of genetic material that controls processes within cells. The "unravelling" occurs during the natural process of cells dying and being replaced by new cells. If a cell's DNA isn't tarnished or unravelled during cell death, the body develops antibodies against it.

"If the TREX1 protein isn't working to disassemble the DNA, you make antibodies to your own DNA and can end up with a disease like lupus," said Perrino.

In a study reported in April in the Journal of Biological Chemistry, Hollis and Perrino found that three variations of the gene decreased the activity of the protein by four- to 35,000-fold.

"Now that we have the structure, we can understand how it disassembles DNA and how mutations in the gene may affect that process," said Hollis.

The researchers hope that comprehending more about the gene's mutations and the structure of the protein may bring about drug treatments to help make sure that mutant copies of the gene are inactive. (ANI)

Viewer's Comment

Comments Not Available

More Stories