How are variations in the APOL1 gene linked to risk of kidney disease?

Our understanding of the role genetics plays in kidney disease has significantly increased in recent years. Variations in more than 500 genes have now been connected to different forms of kidney disease.  Understanding how genetic variations can increase risk of certain chronic kidney diseases presents opportunities for innovation — and holds important clues for investigating potential targeted treatments.

For instance, in 2010, scientists showed that higher rates of severe kidney diseases in people of African descent could be linked to specific changes in a gene called APOL1. Today, Vertex is using this understanding of APOL1 biology to research investigational treatments for APOL1-mediated kidney diseases, including APOL1-mediated focal segmental glomerulosclerosis (FSGS).

What is APOL1?

The APOL1 gene is part of the APOL gene family, which plays a role in innate immunity, our body’s built-in system to fight threats. Everyone has the APOL1 gene, and it’s present in many tissues, including the kidneys.

The story of APOL1 is a story of genetic evolution. Over the past 3,000 to 10,000 years, the gene evolved in specific ways in people who lived in Western and Central Africa to protect them from resistant forms of the parasite that causes African sleeping sickness. So, in areas where this parasite is endemic, having these two genetic variants is actually an advantage, because the variant protein can provide protection from a deadly disease. The plot twist, however, is that those specific changes (or variations) in the APOL1 gene may also put people at increased risk of some genetically linked kidney diseases. Today, these variants are typically found in people of recent African ancestry across the globe, including people who identify as African American, Afro-Caribbean, and Latinx.

Watch the video above to see an illustrated overview of this disease, and how scientists at Vertex Pharmaceuticals Incorporated are approaching the problem.

To learn more about Vertex’s work in APOL1-mediated kidney diseases, visit global.vrtx.com