APOL1 Gene

The APOL1 gene (APOL1 stands for "Apolipoprotein L1") is a protein-coding gene
locatedon chromosome22q12
.3. Several different transcript variants have been found for this gene, coding for different isoforms.

The APOL1 gene encodes the protein apolipoprotein L1 (APOL1), which circulates mainly bound to HDL particles. This circulating fraction of APOL1 confers resistance to trypanosomiasis by rapidly lysing infecting trypanosomes of the species Trypanosoma brucei, trypanosome parasites endemic to Africa. APOL1 is thus an innate immune effector that protects humans from infection by some trypanosome parasites.

Diseases associated with APOL1 include focal segmental glomerulosclerosis 4.

Nucleotide variants/trypanosomiasis resistance: The breakthrough discovery that genetic variations in the APOL1 gene are associated with focal segmental glomerulosclerosis in people of African descent has led to investigation of the biological mechanisms underlying this association (O'Toole JF et al 2017). The high allele frequency of these variants is thought to be due to the resistance they confer to the disease-causing trypanosome species involved in human African sleeping sickness. People of African descent have an increased risk of developing kidney disease, largely due to two variants in the apolipoprotein L1 (APOL1) gene that are unique to people of West African descent. These variants are thought to be genetically dominant because they provide protection against African sleeping sickness, which is caused by the parasite Trypanosoma brucei (Tzur S et al. 2010).

1. O'Toole JF et al (2017) The Cell Biology of APOL1. Seminars in nephrology 37: 538-545.
2. Pays E et al (2014) The molecular arms race between African trypanosomes and humans. Nat Rev Microbiol 12:575-584.
3. Tzur S et al (2010) Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene. Hum Genet 128:345-350.
4. Vanhollebeke B et al. (2008) A haptoglobin-hemoglobin receptor conveys innate immunity to Trypanosoma brucei in humans. Science320:677-681.