The APOL1 gene is a part of human genetic makeup, present in every individual. It plays a role in various biological processes, offering insight into fundamental body functions.
The APOL1 Gene and Its Function
The APOL1 gene is located on chromosome 22, one of the 23 pairs of chromosomes in human cells. This gene provides instructions for making a protein called apolipoprotein L1, or APOL1 protein. Under normal conditions, this protein is involved in the body’s innate immune system, acting as a defense mechanism against certain foreign invaders.
The APOL1 protein circulates in the blood, disrupting the membranes of specific parasites like Trypanosoma brucei rhodesiense, which causes African sleeping sickness. Beyond its immune functions, it also participates in lipid metabolism, influencing how fats are transported and processed.
Common APOL1 Genetic Variants
The APOL1 gene can exist in different forms, known as genetic variants. The most studied variants are G1 and G2, which differ from the common or “wild-type” version of the gene, often referred to as G0. The G1 variant involves two specific changes in the gene’s DNA sequence, while the G2 variant is characterized by a six-nucleotide deletion.
Individuals inherit two copies of the APOL1 gene, one from each parent. A person can inherit no risk variants, one risk variant (G1 or G2), or two risk variants (such as G1/G1, G2/G2, or G1/G2). Inheriting two copies of these specific variants has significant health implications, particularly for kidney function.
APOL1 and Kidney Health
Having two copies of the APOL1 risk variants, either G1/G1, G2/G2, or G1/G2, significantly increases an individual’s susceptibility to developing certain kidney diseases. This genetic predisposition is strongly linked to conditions like Focal Segmental Glomerulosclerosis (FSGS), a disorder that scars the kidney’s filtering units. Another condition, HIV-associated nephropathy (HIVAN), also shows a strong association with these variants, particularly in individuals with HIV.
Furthermore, these variants increase the risk for hypertensive nephrosclerosis, a type of kidney damage caused by high blood pressure. The mechanism by which these variants contribute to kidney injury is thought to involve a toxic effect on kidney cells, particularly the podocytes that are responsible for blood filtration. This can lead to damage and scarring of the kidney’s delicate filtering structures, potentially progressing to kidney failure. While not everyone with two risk copies will develop kidney disease, the likelihood is notably elevated.
Implications for Individuals and Families
The APOL1 risk variants have a disproportionate impact on certain populations, notably individuals of African descent. This is because the variants are believed to have evolved in Western and Central Africa, providing protection against African sleeping sickness, a parasitic infection prevalent in those regions. As a result, people with ancestry from these areas are more likely to carry these genetic forms.
For individuals who carry two copies of the APOL1 risk variants, there are considerations regarding kidney health, including outcomes in kidney transplantation. Genetic testing can identify these variants, and genetic counseling can help individuals understand their risk and make informed decisions about their health. Awareness of these genetic factors can support earlier monitoring and management strategies, potentially helping to slow the progression of kidney disease for those at increased risk.