Scientists Probe Genetic Links to 'Junk Protein' And Obesity

SAN ANTONIO -- A team of scientists has discovered a genetic defect that appears to let junk proteins pile up and cause inflammation inside cells -- a process linked to obesity, diabetes, heart disease and other chronic health problems.

The researchers looked at families in San Antonio and Wisconsin and found that 10 percent to 20 percent had the inflammation-promoting defect.

"We basically have found a brand-new player in inflammation in this gene," said John Blangero, a geneticist at Southwest Foundation for Biomedical Research and the lead author of the study.

Dr. Alan Shuldiner, director of human genetics research at the University of Maryland College of Medicine, who was not involved in the study, said the findings are "very compelling."

"The idea of finding a genetic link to inflammation can make a lot of sense and could be a significant finding," he said.

The findings were published Sunday in the online edition of Nature Genetics and included scientists from San Antonio, Wisconsin and Australia.

Researchers everywhere have been trying to understand why cellular inflammation precedes the onset of complex diseases such as cancer, diabetes, Alzheimer's and heart disease.

The San Antonio-based team was following up on an Australian study that identified a gene called SEPS1 and linked it to higher rates of obesity and diabetes in a species of rat. The U.S.

researchers looked first at people of primarily northern European descent enrolled in a family study at the Medical College of Wisconsin. There they identified a form of the gene, or mutation, that was associated with higher rates of inflammation among the study participants.

Scientists later found the mutation among some subjects in the San Antonio

Family Heart Study, a research project looking at the genetics of heart disease, diabetes and obesity among 1,400 Mexican Americans from 90 San Antonio families.

Genetic analyses uncovered the role of the SEPS1 gene -- it produces a protein that appears to direct cleansing of misfolded proteins that build up when cells are exposed to stress.

"We have all these proteins within the cells in the body, and if they fold incorrectly, they become garbage," said Joanne Curran, a former scientist with

ChemGenex Pharmaceuticals of Australia and now with Southwest Foundation for

Biomedical Research. "This gene assists in breaking them down and moving them out and keeping the cell clean from this kind of garbage.

"When the gene is not working properly, these misfolded proteins build up in the cell because there is nothing to get rid of them," Curran said.

About 10 percent of the Wisconsin subjects and 20 percent of the Mexican-

American subjects had the mutation. But scientists cautioned that this finding doesn't explain why Mexican Americans appear to be more prone to certain chronic conditions such as diabetes.

Shuldiner, of the University of Maryland College of Medicine, who studies the genetics of obesity, heart disease and diabetes among the Amish, said the finding could provide insights into the inflammatory processes that underlie many chronic diseases.

"The next step, of course, is to see how you can intervene.

Sometimes that is an easy step, and sometimes it is a very hard step," he said. Blangero, of Southwest Foundation for Biomedical Research, said the finding would launch a "cottage industry" of new scientific inquiries into this gene and potential targets for drugs. "We are starting those studies now," he said. "We are going to start looking for its downstream effects on the diseases themselves."

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(E-mail: ctumiel@express-news.net)