U.S. Department of Health and Human Services

Genetic factors in kidney and cardiovascular disease

​Variants in the APOL1 gene are associated with increased risk of kidney disease but not cardiovascular disease in African Americans with high blood pressure. Previous studies have shown that African Americans with two copies of certain variants of the APOL1 gene are at increased risk of developing kidney disease from causes other than diabetes, but there have been conflicting data regarding the role of APOL1 in cardiovascular disease.

Elevated blood pressure is relatively common in the U.S. population and is a risk factor for heart disease, stroke, and kidney disease. The Systolic Blood Pressure Intervention Trial (SPRINT) is testing whether reducing systolic blood pressure to a lower goal than currently recommended will reduce cardiovascular disease risk in people with high blood pressure but not diabetes. (“Systolic” refers to the higher of the two numbers in a blood pressure reading; it measures the pressure in the arteries when the heart beats. “Diastolic” refers to the lower of the two numbers and measures the blood pressure when the heart rests between beats).

Over 2,500 African American volunteers in the SPRINT study agreed to undergo genetic testing to allow researchers to examine their APOL1 status as it related to their kidney function and risk of developing cardiovascular disease. Researchers found that study participants with two risk variants of the APOL1 gene were more likely to have mild kidney disease, defined as diminished filtering capacity and/or protein in their urine, than people with a single risk variant or none. However, they were not more likely to have cardiovascular disease.

These data from the SPRINT study add to information learned over the past few years about the contribution of genetic factors to the increased risk of non-diabetic kidney disease in African Americans. The current investigation confirms that the presence of these variants is associated with mild kidney disease in this population but shows that they are not associated with cardiovascular disease. Although a key priority in treating high blood pressure is to reduce the risk of both kidney and cardiovascular disease, more research is needed to identify the role played by APOL1 variants in these two processes.

Langefeld CD, Divers J, Pajewski NM, Hawfield AT, Reboussin DM, Bild DE, Kaysen GA, Kimmel PL, Raj DS, Ricardo AC, Wright JT Jr, Sedor JR, Rocco MV, Freedman BI; Systolic Blood Pressure Intervention Trial (SPRINT). Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial. Kidney Int 87:169-75, 2015.