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Genetics and Kidney Disease

Some diseases are said to run in the family, when more than one person in a family has the same kind of illness. And it’s true, some diseases and conditions, such as sickle cell anemia, that can affect multiple family members, are caused by gene variants (also known as mutations) and can be inherited (passed down from parent to child).

However, there are other diseases and conditions that appear to run in families but are not always caused by the variants in a person’s genes. Instead, environmental factors and individual choices such as dietary habits, pollutants, or a combination of genetic and environmental factors can be the reason why a disease develops.

Genetic variants and kidney disease risk

There are some genetic variations in MYH9 and APOL1 genes that are linked to an increased risk of developing kidney disease, especially in under-resourced communities of color.1-4

APOL1 variants and increased likelihood of kidney disease

APOL1 Variants Leading to Increased Likelihood of Kidney Disease Development

The APOL1 risk variant does not seem to increase the risk of developing diabetic kidney disease, however it does appear to increase the risk of end-stage kidney disease in people with high blood pressure by 7 to 11 times.

APOL1 risk variants also increased the incidence of focal segmental glomerulosclerosis (FSGS) by 17 times, HIV-associated nephropathy (kidney disease caused by HIV) by 29 to 89 times and nondiabetic kidney disease by 2 to 4 times, as well as increases in the development of other kidney diseases.

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However, not all people with these genetic variations develop kidney disease. And people can still develop kidney disease without any genetic variant.

So why do people with certain genetic variants develop kidney disease?

We know that genetic variants are not solely responsible for the development of kidney disease. There are other factors that contribute to your kidney disease risk.

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For many, the risk of developing kidney disease is not because of any one single reason, but due to a number of factors.

Environmental and social factors play a role in influencing and changing the way genes work. Some of the different types of factors include having more than one disease (for example, high blood pressure or diabetes), where you live, work, and play.

While all these factors present challenges and obstacles to good health, there are also individual decisions and personal choices, which contribute to an increased risk of developing kidney disease. Some of these personal decisions include choosing to smoke, not being physically active or exercising, eating unhealthy foods, ignoring your mental health, and other individual behaviors and choices you make in your everyday life.

The illustration below shows how genetic variants, when combined with other factors, can increase your risk of developing several types of kidney diseases.

Factors contributing to kidney disease

Factors contributing to kidney disease venn diagram
*Source: Wanner N, Bechtel-Walz W. Epigenetics of kidney disease. Cell Tissue Res. 2017 Jul;369(1):75-92. doi: 10.1007/s00441-017-2588-x. Epub 2017 Mar 13. PMID: 28286899.

While more research is needed, it’s important that we understand the large role genetics and other factors play in the development of kidney disease. While a genetic variant may put someone at increased risk for kidney disease, there are other factors that are likely to be the trigger for disease development to begin.

References:

  1. Dummer PD, Limou S, Rosenberg AZ, et al. APOL1 kidney disease risk variants—an evolving landscape. Semin Nephrol. 2015;35:222-236.
  2. Kao WH, Klag MJ, Meoni LA, et al. MYH9 is associated with nondiabetic end-stage renal disease in African Americans. Nat Genet. 2008;40:1185-1192.
  3. Leak TS, Perlegas PS, Smith SG, et al. Variants in intron 13 of the ELMO1 gene are associated with diabetic nephropathy in African Americans. Ann Hum Genet. 2019;73:152-159.
  4. Guan M, Keaton JM, Dimitrov L, et al. An exome-wide association study for Type 2 diabetes–attributed end-stage kidney disease in African Americans. Kidney Int Rep. 2018;3:867-878.
  5. Cañadas-Garre M, Anderson K, Cappa R, et al. Genetic susceptibility to chronic kidney disease—some more pieces for the Heritability Puzzle. Front Genet. 2019;10:453.
Date Reviewed: 10-06-2021