APOL1 Genotyping Assay
African Americans have a much higher rate of non-diabetic end-stage renal disease (ESRD) than populations without recent African ancestry. Almost all of this increased risk is associated with two DNA sequence variants in the APOL1 gene designated G1 and G2. The G1 and G2 alleles are mutually exclusive, never occurring on the same copy of the chromosome, and therefore these risk alleles show an autosomal recessive pattern of inheritance. The inheritance of two risk alleles, either G1/G1, G2/G2, or G1/G2, are required to confer the additional risk of kidney disease, which is characterized by a 7- to 10- increased risk for hypertension-associated end-stage renal disease; 10- to 17- fold increased risk for focal segmental glomerulosclerosis, and a 29- fold increased risk for HIV-associated nephropathy. APOL1 risk variants are also associated with progression to ESRD in African American patients with lupus nephritis. There is no statistically significant difference between the risk of kidney disease in individuals with no risk alleles as compared to those with only one risk allele. The APOL1 G1 and G2 risk alleles are very common in African Americans (30% allele frequency) due to evolutionary selection for their protective effect against parasitic trypanosome infection (African sleeping disease), but are rare in non- African chromosomes.
Findings on renal biopsy which suggest the presence of APOL1 risk alleles include collapsing glomerulopathy in patients with nephrotic syndrome. Histopathologic findings in patients with chronic kidney disease which suggest the presence of APOL1 risk alleles include solidified glomeruli, thyroidization-type tubular atrophy, and microcystic tubular dilatation.
Reasons for Testing:
Detection of c.1024A>G; p.Ser342Gly (rs73885319)* and c.1169delTTATAA; p.Asn388_Tyr389del (rs71785313) risk alleles
- Determining risk status in an African American patient, particularly in patients with SLE, membranous glomerulopathy, or HIV
- Patient being considered for kidney donation
- Determination of carrier status in a family member
- Biopsy findings which suggest APOL1 risk alleles (see above)
*The G1 risk allele is comprised of two single nucleotide variants c.1024A>G; p.Ser342Gly (rs73885319) and c.1152T>G; p.Ile384Met (rs60910145) which are in near perfect disequilibrium (i.e. occur together in the vast majority of the time), and risk of disease appears to be predominantly related to the presence of c.1024A>G; p.Ser342Gly (rs73885319). We do not test for the c.1152T>G; p.Ile384Met (rs60910145) with this assay.
Method: real-time PCR (end point analysis)
Turnaround time: same-day
Acceptable specimens include:
Peripheral blood (preferred): At least 2 ml in Lavender top (EDTA) tube Shipped overnight at room temperature
Renal biopsy tissue, fresh frozen: Transport overnight in frozen state (dry-ice) M-Th
Previously extracted DNA: 10ul suspended in TE buffer at 10-100ng/ul
Transport overnight in a frozen state (dry-ice) M-Th
Samples must have two patient identifiers, preferably the patient’s name and date of birth.
Each sample must be accompanied by a requisition form with the declaration signed by the ordering provider.
Please call Arkana Laboratories to request a kit.
- Genovese G, Friedman DJ, Ross MD, et al. Association of Trypanolytic APOL1 Variants With Kidney Disease In African Americans. Science 2010;329:841-5.
- Kopp JB, Nelson GW, Sampath K, et al. APOL1 Genetic Variants In Focal Segmental Glomerulosclerosis And HIV-Associated Nephropathy. J Am Soc Nephrol 2011;22:2129-37.
- Freedman BI, Langefeld CD, Andringa KK, et al. End-Stage Renal Disease In African Americans With Lupus Nephritis Is Associated With APOL1. Arthritis Rheumatol 2014;55:390-396
- Larsen CP, Beggs ML, Saeed M, et al. Histopathologic Findings Associated With APOL1 Risk Variants In Chronic Kidney Disease. Mod Pathol 2014 Aug 1. Epub ahead of print
- Thomson R, Genovese G, Canon C, et al. Evolution of the Primate Trypanolytic Factor APOL1. Proc Natl Acad Sci USA 2014 May 20;111(20):E2130-E2139. Epub ahead of print
Arkana Laboratories Molecular Division
10810 Executive Center Drive, Suite 100
Little Rock, AR 72211
Phone: (501) 604-2695
Fax: (501) 604-2699
Co-Director: Chris Larsen, MD
Co-Director: Jon D. Wilson, MD
Lab Manager: Marjorie Beggs, PhD