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Home // Dubois Lecturer to Analyze the Expression of APOL1 Variants Among Patients of African Descent

Dubois Lecturer to Analyze the Expression of APOL1 Variants Among Patients of African Descent


3 minutes

Ashira Blazer, MD
Ashira Blazer, MD, MS

African American patients are disproportionately affected by lupus nephritis and disproportionately go on to develop end-stage kidney disease. Compounding this problem, about 13% of those with recent African ancestry also carry apolipoprotein L1 (APOL1) genetic mutations, which can cause severe kidney injury.  Rheumatologist Ashira Blazer, MD, MS, Hospital for Special Surgery, examined these genetic risk factors for descendants of African ancestry to understand how the inflammation of lupus drives the expression of APOL1, therefore increasing the penetrance of this genetic risk factor.

Dr. Blazer will discuss her extensive research in APOL1 and lupus as she delivers this year’s Edmund L. Dubois, MD, Memorial Lecture, “APOL1 High-Risk Genotype in SLE: A Genes in Context Story,” at ACR Convergence on Sunday, Nov. 12, at 12 p.m. in Room 11 A–B of the San Diego Convention Center. It also will be available on demand within 24 hours for registered ACR Convergence 2023 participants.

Studies have revealed that patients with the APOL1 high-risk genotype, defined by carrying two variant allele copies, have increased kidney injury risk by multiple causes, including lupus nephritis.

“APOL1 doesn’t increase the risk of developing lupus nephritis, but if you get lupus nephritis, you’re two to five times more likely to need a kidney transplant or dialysis,” Dr. Blazer explained.

To understand the mechanisms behind this relatively common and impactful variation in APOL1, she analyzed endothelial cells that expressed these variants by adding lupus-relevant inflammatory stimuli like interferon and single-stranded RNAs. 

“If you think about the genetic code like a recipe book, our bodies only make certain recipes when needed,” Dr. Blazer said. “Since the APOL1 protein participates in the immune response, our bodies make significantly more APOL1 when an inflammatory stimulus is added. We found that the cells that carry the variant made significantly more APOL1, and in high-risk genotype cells, accumulated APOL1 injured critical organelles, the mitochondria, and lysosome.”

Understanding the environmental context of the APOL1 variant was also a key component of Dr. Blazer’s work. Genetic variations of APOL1 are conserved in those with African ancestry because they provide an evolutionary advantage against African trypanosomiasis. Therefore, the effects of these APOL1 variants are at least partially environmentally contingent. Those who live in a place with a significant presence of African trypanosomiasis are more likely to survive if they carry APOL 1 variants. Conversely, the variant has a deleterious effect on patients with chronic inflammatory conditions in areas where trypanosomiasis is less prevalent.

Dr. Blazer urged researchers to avoid analyses limited to genetic association without a fuller functional genomics framework. Researchers sometimes reach the problematic conclusion that African Americans have worsened chronic illness because it’s “written in their genes,” making these conditions unavoidable, she explained.

“That’s one takeaway I really want to avoid because it deepens scientific racism. The lesson with APOL1 is that propensity toward disease is plastic,” she said. “There are no bad genes that people are born with that inherently cause them to get sick more than others. People evolve based on their environments and the environments of their ancestors, which makes propensity toward disease very conditional.”

To mitigate the potentially harmful effects of APOL1 mutation, Dr. Blazer explained that researchers may need to adopt a different perspective than usual. Often, rheumatologists focus heavily on the immunologic perspective when considering how immune pathways are damaging organ systems. In this case, the immune response is not different, but the organs themselves have a higher propensity towards injury, given the presence of an immune response. 

“All things considered equal on the inflammatory side, there may be risk factors for damage or tissue injury that has to do with the tissue itself,” Dr. Blazer said.


If you weren’t able to attend a session in person during ACR Convergence 2023, you haven’t missed out. All registered meeting participants receive on-demand access to scientific sessions through October 31, 2024.