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APOL1 Kidney Risk Variants and Proteomics.
Teresa K Chen1,2, Aditya L Surapaneni2,3, Dan E Arking4
1Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Summary
The APOL1 risk variants are linked to lower levels of APOL1 and other proteins in the blood. However, these protein changes do not explain the increased risk of kidney failure associated with APOL1.
Area of Science:
- Nephrology
- Genetics
- Proteomics
Background:
- The APOL1 (Apolipoprotein L1) gene variants G1 and G2 are associated with kidney disease in Black adults, presenting with varied clinical outcomes.
- While APOL1 risk variants show cytotoxicity in experimental models, their connection to the circulating proteome remains under-investigated.
Purpose of the Study:
- To investigate the association between APOL1 risk variants and the serum proteome in African American individuals.
- To determine if identified proteins mediate the risk of kidney failure conferred by APOL1 variants.
Main Methods:
- A cross-sectional study analyzed serum proteins (using SOMAscan) from 461 participants in the African American Study of Kidney Disease and Hypertension (AASK).
- Linear regression models assessed associations between APOL1 risk variants and 6790 serum proteins, adjusting for covariates.
- Findings were replicated in 875 Black participants from the Atherosclerosis Risk in Communities (ARIC) study.
Main Results:
- In the AASK cohort, APOL1 risk alleles were associated with significantly lower levels of APOL1, APOL2, CLSTN2, MMP-2, SPOCK2, and TIMP-2.
- Replication in the ARIC cohort showed associations with APOL1, and additionally MMP-2 and TIMP-2 in an additive model.
- APOL1 high-risk status correlated with a 1.6-fold increased risk of kidney failure in AASK, but none of the identified proteins mediated this risk.
Conclusions:
- APOL1 risk variants are strongly associated with reduced circulating levels of APOL1 and other proteins.
- Despite these proteomic associations, none of the identified proteins mediated the kidney failure risk linked to APOL1 variants.
- APOL1 protein levels themselves were not associated with kidney failure risk in either study cohort.
Keywords:
AASK (African American Study of Kidney Disease and Hypertension)apolipoprotein L1chronic kidney diseaseend stage kidney diseaseepidemiology and outcomesgenetic renal diseaseproteomicsrenal function declineMore Related Videos
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