Ten years in: APOL1 reaches beyond the kidney

Joshua S. Waitzman; Jennie Lin

doi:10.1097/MNH.0000000000000511

Ten years in: APOL1 reaches beyond the kidney

Joshua S. Waitzman, Jennie Lin^*

^*Corresponding author for this work

Medicine, Nephrology Division

Research output: Contribution to journal › Review article › peer-review

1 Scopus citations

Abstract

Purpose of reviewAPOL1 nephropathy risk variants drive most of the excess risk of chronic kidney disease (CKD) seen in African Americans, but whether the same risk variants account for excess cardiovascular risk remains unclear. This mini-review highlights the controversies in the APOL1 cardiovascular field.Recent findingsIn the past 10 years, our understanding of how APOL1 risk variants contribute to renal cytotoxicity has increased. Some of the proposed mechanisms for kidney disease are biologically plausible for cells and tissues relevant to cardiovascular disease (CVD), but cardiovascular studies published since 2014 have reported conflicting results regarding APOL1 risk variant association with cardiovascular outcomes. In the past year, several studies have also contributed conflicting results from different types of study populations.SummaryHeterogeneity in study population and study design has led to differing reports on the role of APOL1 nephropathy risk variants in CVD. Without consistently validated associations between these risk variants and CVD, mechanistic studies for APOL1's role in cardiovascular biology lag behind.

Original language	English (US)
Pages (from-to)	375-382
Number of pages	8
Journal	Current opinion in nephrology and hypertension
Volume	28
Issue number	4
DOIs	https://doi.org/10.1097/MNH.0000000000000511
State	Published - Jul 1 2019

Funding

FIGURE 1. APOL1 mRNA expression across tissue and cell type. (a) Normalized APOL1 expression by RNA sequencing of different human tissues. **Denotes kidney expression. Adapted from gtexportal.org. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from: the GTEx Portal on 01/15/19 (b) Single-cell RNA sequencing dot plots representing relative APOL1 expression in different cell types of the kidney, adapted from online database curated at humphreyslab.com., originally from https:// www.ncbi.nlm.nih.gov/pubmed/29980650. CD, collecting duct; DCT, distal convoluted tubule; EC, endothelial cell; IC, intercalated cell; LH or LOH, loop of Henle; Mono, monocytes; PC, principal cell; PT, proximal tubule. J.L. is supported by NIH K08 HL135348.

Keywords

APOL1
cardiovascular
genetics

ASJC Scopus subject areas

Nephrology
Internal Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1097/MNH.0000000000000511

Cite this

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title = "Ten years in: APOL1 reaches beyond the kidney",

abstract = "Purpose of reviewAPOL1 nephropathy risk variants drive most of the excess risk of chronic kidney disease (CKD) seen in African Americans, but whether the same risk variants account for excess cardiovascular risk remains unclear. This mini-review highlights the controversies in the APOL1 cardiovascular field.Recent findingsIn the past 10 years, our understanding of how APOL1 risk variants contribute to renal cytotoxicity has increased. Some of the proposed mechanisms for kidney disease are biologically plausible for cells and tissues relevant to cardiovascular disease (CVD), but cardiovascular studies published since 2014 have reported conflicting results regarding APOL1 risk variant association with cardiovascular outcomes. In the past year, several studies have also contributed conflicting results from different types of study populations.SummaryHeterogeneity in study population and study design has led to differing reports on the role of APOL1 nephropathy risk variants in CVD. Without consistently validated associations between these risk variants and CVD, mechanistic studies for APOL1's role in cardiovascular biology lag behind.",

keywords = "APOL1, cardiovascular, genetics",

author = "Waitzman, {Joshua S.} and Jennie Lin",

note = "Funding Information: FIGURE 1. APOL1 mRNA expression across tissue and cell type. (a) Normalized APOL1 expression by RNA sequencing of different human tissues. **Denotes kidney expression. Adapted from gtexportal.org. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from: the GTEx Portal on 01/15/19 (b) Single-cell RNA sequencing dot plots representing relative APOL1 expression in different cell types of the kidney, adapted from online database curated at humphreyslab.com., originally from https:// www.ncbi.nlm.nih.gov/pubmed/29980650. CD, collecting duct; DCT, distal convoluted tubule; EC, endothelial cell; IC, intercalated cell; LH or LOH, loop of Henle; Mono, monocytes; PC, principal cell; PT, proximal tubule. Funding Information: J.L. is supported by NIH K08 HL135348. Publisher Copyright: {\textcopyright} 2019 Lippincott Williams and Wilkins. All rights reserved.",

year = "2019",

month = jul,

day = "1",

doi = "10.1097/MNH.0000000000000511",

language = "English (US)",

volume = "28",

pages = "375--382",

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T1 - Ten years in

T2 - APOL1 reaches beyond the kidney

AU - Waitzman, Joshua S.

AU - Lin, Jennie

N1 - Funding Information: FIGURE 1. APOL1 mRNA expression across tissue and cell type. (a) Normalized APOL1 expression by RNA sequencing of different human tissues. **Denotes kidney expression. Adapted from gtexportal.org. The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from: the GTEx Portal on 01/15/19 (b) Single-cell RNA sequencing dot plots representing relative APOL1 expression in different cell types of the kidney, adapted from online database curated at humphreyslab.com., originally from https:// www.ncbi.nlm.nih.gov/pubmed/29980650. CD, collecting duct; DCT, distal convoluted tubule; EC, endothelial cell; IC, intercalated cell; LH or LOH, loop of Henle; Mono, monocytes; PC, principal cell; PT, proximal tubule. Funding Information: J.L. is supported by NIH K08 HL135348. Publisher Copyright: © 2019 Lippincott Williams and Wilkins. All rights reserved.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Purpose of reviewAPOL1 nephropathy risk variants drive most of the excess risk of chronic kidney disease (CKD) seen in African Americans, but whether the same risk variants account for excess cardiovascular risk remains unclear. This mini-review highlights the controversies in the APOL1 cardiovascular field.Recent findingsIn the past 10 years, our understanding of how APOL1 risk variants contribute to renal cytotoxicity has increased. Some of the proposed mechanisms for kidney disease are biologically plausible for cells and tissues relevant to cardiovascular disease (CVD), but cardiovascular studies published since 2014 have reported conflicting results regarding APOL1 risk variant association with cardiovascular outcomes. In the past year, several studies have also contributed conflicting results from different types of study populations.SummaryHeterogeneity in study population and study design has led to differing reports on the role of APOL1 nephropathy risk variants in CVD. Without consistently validated associations between these risk variants and CVD, mechanistic studies for APOL1's role in cardiovascular biology lag behind.

AB - Purpose of reviewAPOL1 nephropathy risk variants drive most of the excess risk of chronic kidney disease (CKD) seen in African Americans, but whether the same risk variants account for excess cardiovascular risk remains unclear. This mini-review highlights the controversies in the APOL1 cardiovascular field.Recent findingsIn the past 10 years, our understanding of how APOL1 risk variants contribute to renal cytotoxicity has increased. Some of the proposed mechanisms for kidney disease are biologically plausible for cells and tissues relevant to cardiovascular disease (CVD), but cardiovascular studies published since 2014 have reported conflicting results regarding APOL1 risk variant association with cardiovascular outcomes. In the past year, several studies have also contributed conflicting results from different types of study populations.SummaryHeterogeneity in study population and study design has led to differing reports on the role of APOL1 nephropathy risk variants in CVD. Without consistently validated associations between these risk variants and CVD, mechanistic studies for APOL1's role in cardiovascular biology lag behind.

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IS - 4

ER -

Ten years in: APOL1 reaches beyond the kidney

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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