A new research that appeared in an upcoming issue of the Journal of the American Society of Nephrology (JASN) provide insights into the ties between certain genetic variants and kidney disease in African Americans. The genetic association is one of the strongest ever reported for a common disease and these latest study may help improve diagnosis and treatment.
Recent work from several research groups has shown that African Americans have a 4-fold increased risk for chronic kidney disease compared with European Americans and that much of this risk is due to genetic variations in a gene called apolipoprotein L1 (APOL 1). This gene creates a protein that is a component of HDL, or good cholesterol. These variants arose tens of thousands of years ago in sub-Saharan Africa, and so are present in individuals who have recent sub-Saharan African ancestry. Approximately 5 million African Americans are placed at increased risk for kidney disease because most of them carry APOL1 risk variants.
Information on 94 patients with focal segmental glomerulosclerosis (FSGS) were investigates by Jeffrey Kopp, MD (National Institutes of Health) and his colleagues to understand the role of APOL1 variants in a particular form of FSGS. The team found that patients who had APOL1 variants tended to have more advanced disease when they were diagnosed, which fits with prior observations that this genetic form of FSGS progresses rapidly. Previous research has shown that patients with two APOL1 variants respond to glucocorticoids with reductions in urinary protein excretion but they nonetheless may experience progressive loss of kidney function. The present s tudy showed a similar pattern with cyclosporine and mycophenolate mofetil. “New therapies targeting APOL1 injury pathways are needed, as standard therapies do not work for many people with this gene variant,” said Dr. Kopp.
The investigators also found that 72% of self-identified African Americans in the study had APOL1 risk variants, similar to earlier findings. “We also found the APOL1 risk genotype in 2 individuals of Hispanic descent, which is well known, and in 2 individuals who self-identified as White, or European American, which has not been reported before. This last finding suggests that APOL1 risk variants can be present in individuals who self-identify in various ways,” said Dr. Kopp.
In an accompanying editorial, Christopher Larsen, MD (Nephropath) and Barry Freedman, MD, PhD (Wake Forest School of Medicine) write that “the report by Kopp et al. enhances our understanding of a common etiology of the FSGS lesion seen on kidney biopsy in African Americans.” They note, however, that the findings from the trial, although informative, are not encouraging due to the poor outcomes that patients with APOL1 variants often ultimately experience.