2009 Genetics, Human Lupus Biology
Novel Genes Associated with African-American Lupus
That African-Americans are three times more likely than Caucasians to develop lupus and with greater severity is well-known. But we do not know why. With initial grant support from LRI, researcher Dr. Timothy Niewold at the The Mayo Clinic, Rochester, MN has made great headway in uncovering some of the genes that may predispose African Americans to lupus. In 2011 his work gained particular recognition with several published papers and a sizeable grant from the National Institutes of Health.
Dr. Niewold’s initial proposal hypothesized that African-American patients carry genes that cause them to produce higher levels of interferon-alpha, a critical molecule known to drive lupus progression.
Published in August 2011 issue of Arthritis & Rheumatism, Dr. Niewold’s results showed that interferon-alpha levels are indeed higher in African-American lupus patients. Also stemming from original LRI-funded research, Dr. Niewold’s team had previously discovered differences between Caucasians and African Americans in six genes along the biological pathway involved in producing interferon-alpha.
“By studying the genetics of a multi-gene pathway, we can understand what goes wrong and where in the process we can effectively intervene,” said Dr. Niewold. “Our discovery of these genetic factors affecting the production of interferon-alpha should help us individualize treatment in this disproportionately affected patient group.”
The NIH shares Dr. Niewold’s interest in finding the cause for lupus prevalence and severity among African Americans, awarding him an RO1 grant of $1.95 million to extend his LRI work on a large scale. The five-year study will look deeper into how inherited genetic abnormalities in the interferon-alpha pathway might contribute to lupus in African Americans and other populations.
The goal: information that will enable physicians to individualize and improve treatment for African Americans with lupus.
Influenza vaccination responses in human systemic lupus erythematosus: Impact of clinical and demographic features. Crowe SR, Merrill JT, Vista ES, Dedeke AB, Thompson DM, Stewart S, Guthridge JM, Niewold TB, Franek BS, Air GM, Thompson LF, James JA. Arthritis Rheum. 2011 Aug;63(8):2396-406. doi: 10.1002/art.30388.
Network analysis of associations between serum interferon-α activity, autoantibodies, and clinical features in systemic lupus erythematosus. Arthritis Rheum. 2011 Apr;63(4):1044-53. doi: 10.1002/art.30187. Weckerle CE, Franek BS, Kelly JA, Kumabe M, Mikolaitis RA, Green SL, Utset TO, Jolly M, James JA, Harley JB, Niewold TB.
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Rev. March 2012