Precision Diagnosis in APOL1 Kidney Disease With the p.N264K M1 Protective Variant - PubMed
12 hours ago
- #Kidney Disease
- #Genetic Variant
- #APOL1
- The APOL1 M1 (p.N264K) variant protects against G2-associated APOL1 focal segmental glomerulosclerosis (FSGS) and chronic kidney disease (CKD).
- The study aimed to test two hypotheses: (1) M1 can distinguish APOL1 CKD from non-APOL1 CKD in patients with APOL1 high-risk (HR) genotype kidney disease with at least one G2 allele; (2) M1 is independently associated with protection against FSGS and CKD in people with APOL1 low-risk (LR) genotypes.
- A retrospective case-control study was conducted using data from two tertiary care hospitals and population-based data from UK Biobank, eMERGE-III, and All of Us.
- The study included 107,696 individuals, with 54,994 females, and diverse ancestry backgrounds (African, European, and multiethnic).
- In the APOL1-HR group, M1 was significantly inversely associated with FSGS or SRNS cases compared with controls without kidney disease (OR, 0.20; 95% CI, 0.04-0.63; P = 3.69 × 10-3).
- Among individuals with CKD and APOL1-HR genotypes, M1 was four times more frequent in those whose CKD was not due to FSGS or SRNS.
- Electronic health record and biopsy review identified an alternative, non-APOL1 cause for CKD in nearly all APOL1-HR-M1 cases.
- No association was found between individuals with APOL1-LR genotypes with M1 and protection against CKD or FSGS.
- The presence of an APOL1-HR genotype M1 was significantly associated with protection against kidney disease, suggesting its role as a genetic modifier.
- Patients with CKD and an APOL1-HR genotype and M1 should be evaluated for alternative and potentially treatable causes of their CKD.