APOL1 high-risk genotype — two risk alleles (G1 + G2)
An APOL1 high-risk genotype — two risk alleles in some combination.
You have two copies of a higher-risk APOL1 version (in some combination of the G1 and G2 forms).
Two APOL1 risk alleles substantially increase the lifetime risk of focal segmental glomerulosclerosis, hypertension-attributed chronic kidney disease, and HIV-associated nephropathy. Most carriers still do not develop kidney disease, but blood pressure control and regular kidney function checks are particularly important.
Having two copies substantially raises your lifetime risk of several kinds of kidney disease. Most people with this combination still don't develop kidney problems, but controlling blood pressure and having your kidney function checked regularly are particularly worthwhile.
What this means
APOL1 acts recessively: carrying two risk alleles in any combination — G1/G1, G1/G2, or G2/G2 — produces a several-fold increased risk of several forms of kidney disease. Carrying one of each (G1/G2) gives similar risk to homozygous G1/G1 or G2/G2. This is one of the strongest common genetic variants for kidney disease in people of recent sub-Saharan African ancestry.
APOL1 only causes trouble when you have two copies of the higher-risk version. There are two flavours of that version, called G1 and G2 — and having any pair of them (two G1s, two G2s, or one of each) produces a several-fold higher risk of certain kidney diseases. Carrying one of each is just as impactful as carrying two of the same. This is one of the strongest common DNA changes affecting kidney health in people with recent sub-Saharan African ancestry.
Caveats
- Most carriers of two risk alleles do not develop kidney disease.
- Blood pressure and diabetes control remain the dominant modifiable factors.
- Discussion with a nephrologist is appropriate, especially before kidney donation.