Black Lupus Patients with APOL1 Gene Variants Face Higher Atherosclerosis Risk

Genes found in African-Americans with systemic lupus erythematosus (SLE) may explain why they have a higher risk of atherosclerosis, a heart disease in which fatty deposits can clog arteries.

The study arriving at that conclusion, “Apolipoprotein L1 risk variants associate with prevalent atherosclerotic disease in African American systemic lupus erythematosus patients,” appeared in the journal PLOS|One.

Apoliprotein L1 (APOL1) is one of the protein components of high-density lipoprotein (HDL) or “good cholesterol.” The gene that codes for APOL1 has two other variants, called G1 and G2, which are thought to be more prevalent in people of African descent.

While the variants protect African-Americans from infection by the parasite Trypanosoma brucei, they also raise the risk of  kidney disease. And, as this study shows, black lupus patients who carry these variants may be at higher risk of developing atherosclerotic cardiovascular disease (AsCVD).

People carry two genes, called alleles, for APOL1, which can differ from each other. This study’s authors call G1 and G2 “risk alleles” (RAs) because they occur more often in people with certain diseases.

The study looked at whether lupus patients had no G1 or G2 versions of the APOL1 gene, only one G1 or G2 gene, or two genes, and assessed the percentage of each group that also had atherosclerosis.

Of the 113 study participants, atherosclerotic disease was found in 13.2 percent of those with no risk alleles, 41.7 percent of those with one risk allele, and 60 percent of those with two risk alleles.

This showed a clear association between the APOL1 risk alleles, G1 and G2, and the occurrence of atherosclerosis in black lupus patients. Researchers suggest that because these variants had already been associated with atherosclerosis in the general African-American population, lupus may further aggravate the problem.

“There was a relationship between the risk allele and the percentage of patients affected by atherosclerotic disease, supporting our hypothesis that the risk allele confers a propensity toward vascular dysfunction,” the team stated. “Taken together, the APOL1 RAs associate with prevalent atherosclerotic [cardiovascular disease] in this cohort of SLE patients, perhaps reflecting a potentiating effect of SLE on APOL1-related cardiovascular phenotypes.”