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Home - Diseases - Genetics show possible explanation for lupus disparity

Genetics show possible explanation for lupus disparity

March 14, 2013

Scientists at OMRF think they may have found a gene responsible for developing lupus. Their findings also may explain why the disease tends to occur more often in people of African-American heritage.

African Americans are about 5 times more likely to develop lupus than people of European-American descent, said OMRF researcher Swapan Nath, Ph.D.

Lupus is a chronic autoimmune disease in which the body’s immune system confuses healthy cells with foreign substances, like viruses and bacteria, and attacks the body’s tissues and organs. The disease affects an estimated 2 million Americans and 5 million people worldwide. Around 90 percent of those diagnosed with lupus are women, and it is 2-3 times more prevalent in women of color, like African Americans, Asians, Hispanics and American Indians.

The results, which came from a large collaborative study led by Nath, were published in a paper in the February issue of PLOS Genetics. To pinpoint the gene, called IFIH1, scientists employed a novel statistical method called “admixture mapping,” which uses ancestry-informative markers, or AIMs, and genetic testing to correlate lupus with ancestry.

“We weren’t the first to find the gene, which has previously been linked to other autoimmune diseases like type 1 diabetes,” he said. “But we are the first to show that ancestry plays a statistically significant role in the genetic risk of developing lupus in African Americans.” Ironically, in this case, the IFIH1 risk alleles are linked with European ancestry.

By tracking the genetic ancestry throughout the entire human genome using hundreds of AIMs from more than 20,000 DNA samples from two ethnic groups (African and European), Nath and his research team were able to explain how ancestry can increase the risk of lupus in African Americans.

Statistically, IFIH1 stood out, and when his team examined the gene further through experimentation, Nath said they found three mutations associated with the gene that altered apoptosis (programmed cell death), inflammation, and autoantibody production. Autoantibodies are immune system cells that fight against patients’ own bodies.

“Our next step will be to further explore the gene and better understand how changes to it can have repercussions in the rest of the system,” he said.

Howard Hughes Medical Institute scientist Loren Looger, Ph.D., Robert Kimberly from the University of Alabama, John Harley from Cincinnati Children’s, and OMRF researchers Julio Molineros, Ph.D., Amit Maiti, Ph.D., and Celi Sun, M.S., from Nath’s group contributed to the discovery.

Funding for the project was provided by grant No. R01 AR060366-03 and grant No. P01 AR049084-10 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases and grant No. P01 AI083194 from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.

Filed Under: Diseases, News, Research News Tagged With: admixture mapping, African Americans, ancestry, genetic ancestry, genetics, IFIH1, lupus, lupus genetics, Nath, PLOS Genetics, scientist-news, Swapan, Swapan Nath

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