Molecular Genetics APOL1, Sequencing

Compared to individuals without recent African ancestry, African Americans have high rates of kidney disease¹. Two independent polymorphisms in the APOL1 gene have been shown to be likely associated with the following forms of kidney disease: focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) ². The first polymorphism, termed G1, is a two-locus APOL1 polymorphic allele consisting of c.1024A>G; p.Ser342Gly (rs73885319) and c.1152T>G; p.Ile384Met (rs60910145); the second polymorphism, termed G2, is a 6-base pair deletion c.1164_1169delTTATAA (rs71785313). Individuals carrying two risk alleles (G1/G2) have an odds ratio of 7.3 of developing renal disease as compared to individuals carrying neither G1 or G2, while individuals carrying only one risk allele (G1 or G2) have an odds ratio of just 1.26 as compared to individuals carrying neither G1 or G2³. A recessive model of inheritance best explains this finding². These APOL1 risk polymorphisms for kidney disease occur in more than 30% of African-American chromosomes while virtually absent in non-African chromosomes². Natural selection provides a plausible explanation as either of the resulting variant proteins provides heightened Trypanosoma lytic activity for heterozygotes with little increased risk for kidney disease.

Reasons for Referral:
Determination of c.1024A>G, c.1152T>G, and c.1164_1169delTTATAA status:
• Prior to donation of a kidney
• As a limited diagnostic tool
• For determination of carrier status

Targeted gene sequencing of APOL1 exon 6 in which c.1024A>G, c.1152T>G, and c.1164_1169delTTATAA are embedded is performed.

Test reporting follows the ACMG Standards & Guidelines for Clinical Genetics Laboratories.

Blood: EDTA ( purple top) or ACD (yellow top) (Solutions A or B):

• Adult: 5 mL
• Child: 5 mL
• Infant: 2-3 mL

Saliva: 2 ORAgene Saliva Kit(s) (OGR-500)
Skin Fibroblast: Punch Biopsy, or 2 T-25 confluent flasks
DNA: 1-2µg at a minimum of 50-100ng/µL (DNA must be extracted in a CLIA-certified laboratory or a laboratory meeting equivalent requirements as determined by the CAP and/or CMS)

For routine testing of blood, saliva and buccal swabs, KDL does NOT accept samples from patients within two (2) weeks of a packed cell/platelet transfusion or within four (4) weeks of a whole blood transfusion.  For extraordinary circumstances, where testing must be performed outside of the above windows, please contact our lab.

Ethnicity MUST be indicated on requisition.

A REQUISITION FORM MUST ACCOMPANY ALL SAMPLES.  Please include detailed clinical information, including ethnicity, clinical history, and family history.

Weekly

7-14 Days

• Package and ship specimen to remain cold, but not frozen.
• Ship via overnight express, using the FedEx priority overnight label provided.
• Contact Client Services for shipping kits and instructions at (855) 535-1522.

1. S.B. Satko, et al. Kidney Int. suppl 67, (s94), S46 (2005).
2. G. Genovese, et al. Science 329: 841-845 (2010).
3. D. Cohen, et al. Transplantation 92:722-725 (2011)

Prior to any genetic testing we recommend genetic counseling.