The National Institutes of Health has awarded an Oklahoma Medical Research Foundation scientist $2.9 million to better understand how genetic variants contribute to the autoimmune disease lupus.
Scientists discovered the connection between genetic variations and lupus more than half a century ago. However, diagnosing and treating the disease remains challenging, in part because researchers can’t trace it to a single telltale genetic variant, said OMRF scientist Swapan Nath, Ph.D., who received the four-year grant.
“Not only do different genes play roles in lupus, but even when the same variants are shared by two people with lupus, they can exhibit significantly different clinical manifestations,” Nath said.
In lupus, the immune system attacks the body’s own tissues. It can cause damage to the joints, skin, kidneys, heart and lungs.
According to the Lupus Foundation of America, about 1.5 million Americans – primarily women – have the disease. Lupus disproportionately affects African Americans, American Indians, Latinos and Asians, and it tends to be more severe among those ethnicities.
Nath, who holds the William H. & Rita Bell Chair in Biomedical Research at OMRF, will investigate genetic variants sourced from repositories of samples donated by people with lupus worldwide. He expects to identify five to 10 common or ethnicity-specific variants and then focus on those in future research.
“We’re looking for genetic variants that could be affecting a normal and beneficial cellular process known as autophagy, which is like a recycling system within the body,” Nath said. “This process operates daily throughout our body as cells discard defective parts or fight infections.”
Autophagy is essential for maintaining the balance and proper functioning of our cells. When functioning correctly, it safeguards against diseases, but any dysfunction can contribute to disease development.
Recent genome-wide studies conducted by Nath’s lab and others have uncovered a link between autoimmune diseases and variants in genes that control autophagy. Nath’s grant enables him to test his hypothesis that ethnicity-specific variants in those genes predispose a person to lupus.
If successful, future research could focus on how the disease manifests differently through those variants among various ethnicities.
“If Dr. Nath’s hypothesis is correct, this area of study could be a game-changer in lupus research,” said OMRF Chief Medical Officer & Executive Vice President Judith James, M.D., Ph.D. “His research promises to narrow the focus, aiding our understanding of which genetic variants contribute to this disease.”
Nath’s grant, 1R01AI172255-01A1, was issued by the National Institute of Allergy and Infectious Diseases and the National Institute of General Medical Sciences, both part of the NIH. The Oklahoma City-based Presbyterian Health Foundation provided funding for Nath’s preliminary data.