Multiethnic prevalence of the APOL1 G1 and G2 variants among the Israeli dialysis population

Abstract

Background and hypothesis: The two apolipoprotein L1 (APOL1) variants, G1 and G2, are common in populations of sub-Saharan African ancestry. Individuals with two of these alleles (G1 or G2) have an increased risk for a spectrum of non-diabetic chronic kidney diseases. However, these variants are typically not observed outside of populations that self-identify as current continental Africans or having clear recent African ancestry such as, most notably, African Americans, and other large population groups in the Americas and several European countries. We hypothesized that the diverse ethnic groups within the Israeli population may exhibit varying levels of recent African ancestry. Therefore, it is plausible that APOL1 risk alleles might be present even in individuals who do not self-identify as being of sub-Saharan African descent.

Methods: We non-selectively screened people with kidney failure across Israel for APOL1 risk variants using restriction fragment length polymorphism.

Results: We recruited 1744 individuals from 38 dialysis units in Israel. We identified eight patients of Moroccan Jewish, Bedouin, or Muslim Arab ancestry, who carry at least one G1 or G2 allele. None of the eight patients carried the protective APOL1 p.N264K variant. Furthermore, despite all Bedouin individuals being G2 heterozygous, the G2 minor allele frequency was significantly enriched in kidney failure cases compared to ethnically matched controls (P = .006).

Conclusions: These findings show that APOL1 G1 and G2 allelic variants are present in populations previously not appreciated to possess recent sub-Saharan ancestry and suggest that a single G2 risk variant may confer increased risk for chronic kidney disease in certain population contexts.

Keywords: CKD; chronic renal failure; ethnicity; gene polymorphism; podocytes.

Graphical Abstract

Figure 1:

The ethnic and clinical diversity of the Israeli dialysis population. (A) Ethnic identification of 1744 Israeli kidney failure patients. See Methods and Introduction for the named categories of the different ethnic groups. (B) The proportion of cases attributed to common primary kidney diseases within each ethnic group. In both panels, the red dots indicate individuals carrying either APOL1 G1 or G2 alleles. Ethnicity data and primary kidney disease data were not available in 6.99% and 2.92% of the cohort, respectively.