Determining an individual’s APOL1 genotype
This test is not useful for clinical management of individuals with APOL1 risk genotypes.
This test alone is not useful for determining eligibility for donation or receipt of kidney allografts.(12)
Real-Time Polymerase Chain Reaction (PCR) with Allelic Discrimination Analysis
G2
G1
ESRD
End-stage renal disease
CKD
Chronic kidney disease
APOL1
Apolipoprotein L1
Varies
Patient Preparation: A previous hematopoietic stem cell transplant from an allogenic donor will interfere with testing. For information about testing patients who have received a hematopoietic stem cell transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send whole blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
Specimen Type: Cord blood
Container/Tube: Lavender top (EDTA)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send cord blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/Refrigerated 4 days/Frozen 4 days
Additional Information:
1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.
2. To ensure minimum volume and concentration of DNA is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
3. While a properly collected cord blood sample may not be at risk for maternal cell contamination, unanticipated complications may occur during collection. Therefore, maternal cell contamination studies are recommended to ensure the test results reflect that of the patient tested and are available at an additional charge. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
Specimen Type: Saliva
Patient Preparation: Patient should not eat, drink, smoke, or chew gum 30 minutes prior to collection.
Supplies: Saliva Swab Collection Kit (T786)
Specimen Volume: 1 Swab
Collection Instructions: Collect and send specimen per kit instructions.
Specimen Stability Information: Ambient (preferred) 30 days/Refrigerated 30 days
Additional information: Saliva specimens are acceptable but not recommended. Due to lower quantity/quality of DNA yielded from saliva, some aspects of the test may not perform as well as DNA extracted from a whole blood sample. When applicable, specific gene regions that were unable to be interrogated will be noted in the report. Alternatively, additional specimen may be required to complete testing.
Specimen Type: Extracted DNA
Container/Tube:
Preferred: Screw Cap Micro Tube, 2 mL with skirted conical base
Acceptable: Matrix tube, 1 mL
Collection Instructions:
1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.
2. Include concentration and volume on tube.
Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated
Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
2. If not ordering electronically, complete, print, and send a Renal Diagnostics Test Request (T830) with the specimen.
Blood: 0.4 mL
Saliva/DNA: See Specimen Required
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Determining an individual’s APOL1 genotype
This test is not useful for clinical management of individuals with APOL1 risk genotypes.
This test alone is not useful for determining eligibility for donation or receipt of kidney allografts.(12)
The APOL1 gene encodes apolipoprotein L-1, a serum apolipoprotein bound to high-density lipoprotein (HDL) particles. Two alleles, commonly called G1 and G2, have been associated with increased risk for development or progression of nondiabetic chronic kidney diseases (CKD), including HIV-associated nephropathy (HIVAN) and focal segmental glomerulosclerosis (FSGS) with collapsing features.(1-4)
The APOL1 (NM_001136540.1) G1 allele is a haplotype consisting of 2 missense variants: c.1024A>G (p.Ser342Gly) and c.1152T>G (p.Ile384Met). The G2 allele is comprised of a 6 base pair deletion that results in the deletion of 2 amino acids: c.1164_1169del (p.Asn388_Tyr389del). The G1 and G2 alleles are thought to be in complete linkage disequilibrium, meaning when both the G1 and G2 alleles are detected, they are on opposite chromosomes.(1) The risk for chronic kidney disease is only increased when 2 risk alleles are present (ie, genotypes G1/G1, G2/G2, or G1/G2), following an autosomal recessive pattern of inheritance.(1) Individuals with 2 risk alleles and nondiabetic CKD can be described as having APOL1-associated nephropathy. Individuals with one risk allele or no risk alleles do not appear to be at an increased risk for APOL1-associated nephropathy.
The G1 and G2 risk alleles are enriched in individuals of African ancestry. Population studies show that in individuals of African descent, the G1 and G2 alleles occur at a frequency of 20% to 22.5% and 13% to 15%, respectively.(5-6) Importantly, it is estimated that 10% to 15% of individuals of African descent have 2 risk alleles.(5-6) The high frequency of the G1 and G2 alleles in this population is likely due to the protective effect these alleles confer against Trypanosoma brucei ganbiense and Trypanosoma brucei rhodesiense, which are parasites that causes trypanosomiasis, a disease endemic to Africa.(1) The G1 and G2 alleles are extremely rare or absent in individuals not of recent African descent (eg, European and Asian descent).(1,5) For this reason, increased risk associated with the G1 and G2 alleles has only been stratified in populations of recent African ancestry, and it remains unclear if similar risk effects associated with these APOL1 risk genotypes are applicable to individuals without African ancestry.
Currently, there are no guidelines for clinical management of individuals with APOL1 risk genotypes and there are no specific treatments for APOL1-associated nephropathy.(7) However, several clinical trials are underway studying potential treatments.(8) Additionally, there currently is limited guidance on genetic testing strategies for APOL1 risk genotypes.(9) One consensus statement suggests APOL1 genotyping should be considered "in all patients of African ancestry with kidney disease and in any patient with kidney disease and a family member with a confirmed APOL1 high-risk genotype."(7)
Evidence exists that the donor APOL1 genotype may impact both donor and recipient outcomes of kidney allografts. Previous studies have shown that donor kidneys from individuals with 2 risk alleles were more likely to fail after transplantation when compared to donor kidneys from individuals with one or no risk alleles.(10-11) Another study suggests that living donors with two risk alleles may be at an increased risk for reduced kidney function following kidney donation.(12) Recent literature suggests that recipients with 2 APOL1 high risk alleles may have lower graft survival one year after transplantation; however, additional research is required.(13-14) A prospective, large scale study to assess kidney allograft survival from donors with recent African ancestry based on donor and recipient APOL1 genotypes is currently ongoing.(15) Based on presently available data, guidelines advise that an individual's APOL1 genotype alone should not determine eligibility for donation or receipt of kidney allografts.(16)
An interpretive report will be provided.
The interpretive report includes an overview of the findings as well as the associated clinical significance.
This assay will not detect all variants associated with an increased risk for development or progression of a chronic kidney disease. Therefore, the absence of an APOL1 risk genotype does not rule out the possibility that an individual is at an increased risk for development or progression of a chronic kidney disease.
Specific APOL1 genotypes are associated with an increased lifetime risk for chronic kidney diseases. Currently, there are no guidelines for clinical management of individuals with APOL1 risk genotypes.
The APOL1 genotype of a kidney donor may be associated with worsened outcomes in the allograft recipient. However. this assay cannot predict or rule out the development or progression of a chronic kidney disease in an individual. Current guidelines advise that an individual's APOL1 genotype alone should not determine eligibility for donation or receipt of kidney allografts.(12)
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete.
Rare alterations may be present that could lead to false-negative or false-positive results. This assay does not identify less common apolipoprotein L1 alleles. Thus, an individual who appears to be homozygous for G1 or G2 may carry a rare allele that cannot be detected by this assay. If results obtained do not match the clinical findings, additional testing should be considered.
In rare cases, DNA variants of undetermined significance may be identified.
Specimens may contain donor DNA if obtained from patients who received non-leukocyte reduced blood transfusions or allogeneic hematopoietic stem cell transplantation. Results from specimens obtained under these circumstances may not accurately reflect the recipient's genotype. For individuals who have received non-leukocyte reduced blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. For individuals who have received allogeneic hematopoietic stem cell transplantation, a pretransplant DNA specimen is recommended for testing.
1. Genovese G, Friedman DJ, Ross MD, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010;329(5993):841-845. doi:10.1126/science.1193032
2. Parsa A, Kao WH, Xie D, et al. APOL1 risk variants, race, and progression of chronic kidney disease. N Engl J Med. 2013;369(23):2183-2196. doi:10.1056/NEJMoa1310345
3. 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(11):2129-2137. doi:10.1681/ASN.2011040388
4. Larsen CP, Beggs ML, Saeed M, Walker PD. Apolipoprotein L1 risk variants associate with systemic lupus erythematosus-associated collapsing glomerulopathy. J Am Soc Nephrol. 2013;24(5):722-725. doi:10.1681/ASN.2012121180
5. Friedman DJ, Kozlitina J, Genovese G, Jog P, Pollak MR. Population-based risk assessment of APOL1 on renal disease. J Am Soc Nephrol. 2011;22(11):2098-2105. doi:10.1681/ASN.2011050519
6. Duran CE, Ramírez A, Posada JG, et al. Prevalence of APOL1 risk variants in afro-descendant patients with chronic kidney disease in a Latin American Country. Int J Nephrol. 2019;2019:7076326. doi:10.1155/2019/7076326
7. Freedman BI, Burke W, Divers J, et al. Diagnosis, education, and care of patients with APOL1-associated nephropathy: A Delphi consensus and systematic review. J Am Soc Nephrol. 2021;32(7):1765-1778. doi:10.1681/ASN.2020101399
8. Vasquez-Rios G, De Cos M, Campbell KN. Novel therapies in APOL1-mediated kidney disease: from molecular pathways to therapeutic options. Kidney Int Rep. 2023;8(11):2226-2234. doi:10.1016/j.ekir.2023.08.028
9. McIntosh T, Walsh H, Baldwin K, et al. Evaluating ApoL1 genetic testing policy options for transplant centers: A Delphi Consensus Panel project with stakeholders. Clin J Am Soc Nephrol. 2024;19(4):494-502. doi:10.2215/CJN.0000000000000397
10. Reeves-Daniel AM, DePalma JA, Bleyer AJ, et al. The APOL1 gene and allograft survival after kidney transplantation. Am J Transplant. 2011;11(5):1025-1030. doi:10.1111/j.1600-6143.2011.03513.x
11. Freedman BI, Julian BA, Pastan SO, et al. Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure. Am J Transplant. 2015;15(6):1615-1622. doi:10.1111/ajt.13223
12. Doshi MD, Ortigosa-Goggins M, Garg AX, et al. APOL1 genotype and renal function of black living donors. J Am Soc Nephrol. 2018;29(4):1309-1316. doi:10.1681/ASN.2017060658
13. Freedman BI, Mena-Gutierrez AM, Ma L. Recipient APOL1 Genotype Effects on Outcomes After Kidney Transplantation. Am J Kidney Dis. 2022;79(3):450-452. doi:10.1053/j.ajkd.2021.11.001
14. Zhang Z, Sun Z, Fu J, et al. Recipient APOL1 risk alleles associate with death-censored renal allograft survival and rejection episodes. J Clin Invest. 2021;131(22):e146643. doi:10.1172/JCI146643
15. Freedman BI, Moxey-Mims MM, Alexander AA, et al. APOL1 long-term kidney transplantation outcomes network (APOLLO): Design and rationale. Kidney Int Rep. 2019;5(3):278-288. doi:10.1016/j.ekir.2019.11.022
16. Newell KA, Formica RN, Gill JS, et al. Integrating APOL1 gene variants into renal transplantation: Considerations arising from the American Society of Transplantation Expert Conference. Am J Transplant. 2017;17(4):901-911. doi:10.1111/ajt.14173
Genomic DNA is extracted from whole blood. Genotyping for each allele is performed using a polymerase chain reaction (PCR)-based 5'-nuclease assay. Fluorescently labeled detection probes anneal to the target DNA. PCR is used to amplify the section of DNA that contains the variant. If the detection probe is an exact match to the target DNA, the 5'-nuclease polymerase degrades the probe, the reporter dye is released from the effects of the quencher dye, and a fluorescent signal is detected.(Unpublished Mayo method)
Monday through Friday
This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.
81479
| Test Id | Test Order Name | Order LOINC Value |
|---|---|---|
| APOL1 | APOL1 Genotype, V | 104664-8 |
| Result Id | Test Result Name |
Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
|
|---|---|---|
| 610559 | APOL1 Result | 104664-8 |
| 610561 | Interpretation | 69047-9 |
| 610562 | Additional Information | 48767-8 |
| 610563 | Method | 85069-3 |
| 610564 | Disclaimer | 62364-5 |
| 610565 | Reviewed by | 18771-6 |