Understanding APOL1: A Guide for People of African Ancestry

If your family roots trace back to West Africa or Central Africa, you may have heard about a gene called APOL1. This gene has become an important topic of conversation because of how it influences kidney health, especially among people of African ancestry.

What is APOL1?

The APOL1 gene (short for apolipoprotein L1) is located on chromosome 22 in humans. This gene provides the instructions for making the APOL1 protein, a special protein that helps the body fight infections and manage fats (also known as lipids) in the blood.

Everyone inherits two copies of the APOL1 gene, one from their mother and one from their father. This means your unique combination of APOL1 variants can influence how your body responds to disease and how your kidney health may be affected.

In simple terms, the APOL1 gene acts like a tiny instruction manual inside your DNA that helps your body defend itself, but certain versions of it can also play a role in APOL1-mediated kidney disease, especially in people of African ancestry.

What does the APOL1 protein do?

The APOL1 protein belongs to the apolipoprotein family, which is a group of proteins that carry fats through the bloodstream. It connects with another major protein called apolipoprotein A-I and helps move cholesterol and other lipids around the body to keep cells healthy and functioning properly.

But the APOL1 protein does more than just handle fats. It has an incredible evolutionary story that links directly to African heritage. Thousands of years ago, some populations in West and Central Africa faced a deadly disease called African sleeping sickness, caused by the parasite Trypanosoma brucei and spread by the tsetse fly.

To survive, the body developed protective changes known as APOL1 variants in the gene. These special versions of the APOL1 protein were strong enough to destroy the parasite, giving people a life-saving advantage. Scientists refer to these protective changes as the G1 and G2 variants.

However, this survival advantage came with an unexpected trade-off. While these APOL1 variants helped protect against sleeping sickness, research has shown that inheriting two of them can increase the risk of APOL1 mediated kidney disease later in life.

So, the APOL1 gene tells a powerful story of evolution. The same genetic traits that protected our African ancestors from deadly infections are now linked to modern-day challenges in kidney health.

What Are APOL1 Variants or Risk Alleles?

A variant is simply a different version of a gene. For the APOL1 gene, scientists have identified three main versions called G0, G1, and G2. These versions are also known as APOL1 variants or APOL1 risk alleles.

• G0 is the typical version of the gene without any known risk changes.

• G1 includes two small changes in the genetic code that alter the structure of the APOL1 protein.

• G2 involves the loss of two amino acids in the same part of the protein.

  
  

The G1 and G2 variants became more common among people whose ancestors lived in West Africa and Central Africa. These variants offered a powerful survival advantage because they helped protect against Trypanosoma brucei, the parasite that causes African sleeping sickness.

Over many generations, this advantage allowed the variants to spread widely through African populations.

However, having these variants can also influence kidney health. People who inherit two APOL1 risk variants are more likely to develop APOL1 mediated kidney disease. This includes conditions such as chronic kidney disease (CKD), focal segmental glomerulosclerosis (FSGS), and other forms of non-diabetic kidney disease.

It is important to note that having just one risk variant does not usually increase the risk in the same way. Many people with only one APOL1 variant maintain normal kidney function throughout their lives.

What Is APOL1 Mediated Kidney Disease?

When a person inherits two APOL1 risk variants (for example, G1/G1, G2/G2, or G1/G2), they are said to be at higher risk for a condition known as APOL1 mediated kidney disease.

This condition, sometimes called APOL1 associated kidney disease, refers to a group of kidney disorders that occur more often in people of African ancestry because of their unique APOL1 variants.

These kidney diseases can include:

• Chronic kidney disease (CKD) that is not caused by diabetes.

• Focal segmental glomerulosclerosis (FSGS), a serious disease that scars the kidney’s filtering units (called glomeruli).

• Kidney disease linked to high blood pressure or HIV infection, which tends to appear more often in people who carry two APOL1 variants.

  
  

It is very important to understand that having two APOL1 risk variants does not automatically mean a person will get kidney disease. According to the National Kidney Foundation, about 80 percent of people with two APOL1 variants never develop kidney disease.

However, when APOL1 mediated kidney disease does occur, it often progresses more quickly and may respond less effectively to standard treatments. 

This is why APOL1 genetic testing is becoming an important tool for early awareness and prevention, especially for people with African ancestry who may be at higher risk.

In simple terms, APOL1 mediated kidney disease is about risk, not destiny. Understanding your APOL1 status can help you and your healthcare provider take early steps to protect your kidney health.

Why Does APOL1 Matter Especially for African Ancestry?

If your roots trace back to Africa, especially West or Central Africa, you are more likely to carry one or two APOL1 risk variants. This is because these regions once faced a serious threat called sleeping sickness, a deadly disease spread by tsetse flies.

Long ago, a natural genetic change in the APOL1 gene helped protect people from this parasite. Over generations, these protective variants became more common in African populations.

However, this same change that once helped survival now also increases the risk of certain kidney diseases.

In the United States, for example, about 13% of self-identified African Americans have two APOL1 risk variants. Because of this higher frequency, APOL1 is one of the main genetic factors that helps explain why kidney disease rates are higher among people of African ancestry.

This makes APOL1 an important part of both ancestral identity and modern health awareness. Understanding it helps communities of African descent take control of their health, while also celebrating the strength and resilience built into their genetic heritage.

What Does APOL1 Genetic Testing Mean?

As science learns more about the APOL1 gene, genetic testing is becoming more common and useful. APOL1 genetic testing is a simple test that looks at your DNA to find out whether you have 0, 1, or 2 APOL1 risk variants.

This kind of test helps people understand their genetic risk for APOL1-mediated kidney disease. In some countries, such as the United States, transplant programs may consider a person’s APOL1 status when matching kidney donors and recipients.

What an APOL1 Test Can Tell You

• Whether you carry any APOL1 risk variants.

• If you have two risk variants, it means you are in a higher-risk group for APOL1-mediated kidney disease.

• If you have zero or one risk variant, your risk is much lower from the APOL1 perspective, though not completely absent.

  
  

What an APOL1 Test Cannot Tell You (Yet)

• It cannot predict exactly whether you will develop kidney disease, since other factors like blood pressure, infections, lifestyle, and environment also play major roles.

• It is not yet a standard test everywhere. Researchers and health professionals are still discussing the best ways to use this information in clinical care.

• A positive result (having two risk variants) is not a diagnosis. It is a signal to monitor your kidney health early in order to make informed lifestyle choices.

What can people of African descent do with this knowledge?

Because APOL1 matters especially for African ancestry, here are some actions and reflections:

1. Know your family history: If there is a history of kidney disease in your family (especially non-diabetic kidney disease) this may prompt discussion with a doctor about APOL1 and kidney risk.

   
   

2. Talk to a healthcare provider: If you belong to a high-risk ancestry group (West/Central Africa descent) ask about kidney health, blood pressure control, and whether APOL1 testing might be appropriate for you.

   
   

3. Healthy kidney habits:

   a. Keep blood pressure in good control.

   b. Maintain healthy weight and diet.

   c. Avoid exposures that stress the kidneys (e.g., certain drugs, toxins).

   d. Monitor kidney function periodically (check urine for protein, check estimated glomerular filtration rate (eGFR)).

   
   

4. Get genetic testing: If you choose APOL1 genetic testing and find you have 2 risk variants, work with your doctor to make a ‘plan’ for monitoring and early detection rather than waiting for problems to show up.

   
   

5. Heritage awareness: Understanding that this gene version evolved in Africa to protect against a parasite gives a powerful story of how our ancestry connects to health in modern times. It can empower communities of African descent to engage in genetic and ancestral health discussions informed by their heritage.

   
   

Knowing Your Genes, Protecting Your Health

The story of APOL1 beautifully shows how our genetic past connects to our present health. For people of African ancestry, the presence of APOL1 risk variants is not a life sentence. Instead, it is valuable information that can guide you toward better health decisions.

Understanding your APOL1 genetic status allows you to take early action, monitor your kidney health, and make choices that are informed by both heritage and science.

If you have ever wondered how your ancestry, your genes, and your health come together, APOL1 offers a meaningful example. It reminds us about the interconnectedness of ancestry and health.

As research continues, new discoveries and better tools will help communities of African descent use this knowledge to improve health outcomes.

Remember, genetics is only one part of the story. Your lifestyle, environment, diet, and access to healthcare all play powerful roles in your well-being.