APOL1: Why Is It Important?

I have been working at Arkana Laboratories (formerly Nephropath) for close to seven years as the Molecular Diagnostics Laboratory Supervisor. One of my first projects here was to isolate DNA from formalin-fixed, paraffin-embedded tissue and get an assay set up to determine variants in the APOL1 gene. At that time, these variants were recently discovered and there was great excitement in the scientific community as to their role in kidney disease, especially in African Americans, which is the population with the highest frequency of these gene variants in America. Our project involved the role of these variants in collapsing glomerulopathy in people suffering from systemic lupus erythematosus, which is an autoimmune disease. Our published results indicated that the presence of the variants associated strongly with collapsing glomerulopathy in this population. Other kidney diseases have also been found to have a worse prognosis when these variants are present.

APOL1 is an important gene in kidney disease. Two variants in this gene have been found to compromise kidney function in some individuals. These variations are more frequently found in individuals with West African ancestry. These APOL1 variants evolved over time in people from West Africa as they protected them from the organism that causes sleeping sickness when only one copy was present. Unfortunately, this comes at the expense of kidney disease in patients who inherit two copies and can lead to the need for a kidney transplant. Approximately 30% of African Americans carry one or more of these variants.

So how does this impact the African American community? First, we know very little about the function of APOL1 in the kidney. Some individuals that have two variants succumb to kidney disease (often focal segmental glomerulosclerosis) after viral infections and other environmental signals that have not yet been discovered. Yet some people that carry two variants never have kidney problems, despite being at higher risk. We do know that testing for these variations is important when dealing with kidney transplantation as a person receiving a donor kidney with two variants is at a higher risk of losing the donor kidney to failure over time.

I would like to see more funds used to find out more about this gene and its variants. If more was known about why APOL1 variants cause disease in certain patients, we could potentially advise patients on lifestyle or environmental exposures that could be detrimental to their kidney health. Healthcare in the African American community is often underserved and increased knowledge of the role these variants play in kidney disease would potentially result in significant improvements in kidney health in this population, especially if this knowledge were to lead to an intervention or cure for APOL1-mediated kidney disease .

Our APOL1 testing is CAP/CLIA certified and we are one of several sites performing this clinical testing. I am very passionate about spreading the word to anyone who wants to listen about this gene and its consequences for kidney health. Most people respond with interest and amazement and want to know more. I believe that the study of this gene and its variants should be a top funding priority in our healthcare system, as more knowledge could prevent the terrible consequences of APOL1-related kidney failure, which represents a significantly increased burden of kidney disease in the African American community.