APOL1 Kidney Disease Risk Variants: An Evolving Landscape

被引:109
作者
Dummer, Patrick D. [1 ]
Limou, Sophie [2 ]
Rosenberg, Avi Z. [1 ,3 ]
Heymann, Jurgen [1 ]
Nelson, George [2 ]
Winkler, Cheryl A. [2 ]
Kopp, Jeffrey B. [1 ]
机构
[1] NIDDK, NIH, Kidney Dis Branch, Bethesda, MD USA
[2] NCI, Ctr Canc Res, Mol Epidemiol Genet Sect, Frederick, MD 21701 USA
[3] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA
基金
美国国家卫生研究院;
关键词
Health disparities; chronic kidney disease; focal segmental glomerulosclerosis; innate immunity; APOL1; TRYPANOSOME LYTIC FACTOR; APOLIPOPROTEIN-L GENE; LIPID-BINDING PROTEIN; STAGE RENAL-DISEASE; TRYPANOLYTIC FACTOR; AFRICAN-AMERICANS; CARDIOVASCULAR-DISEASE; PLASMA TRIGLYCERIDES; INNATE IMMUNITY; MESSENGER-RNA;
D O I
10.1016/j.semnephrol.2015.04.008
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Apolipoprotein L1 (APOL1) genetic variants account for much of the excess risk of chronic and end-stage kidney disease, which results in a significant global health disparity for persons of African ancestry. We estimate the lifetime risk of kidney disease in APOL1 dual-risk allele individuals to be at least 15%. Experimental evidence suggests a direct role of APOL1 in pore formation, cellular injury, and programmed cell death in renal injury. The APOL1 BH3 motif, often associated with cell death, is unlikely to play a role in APOL1-induced cytotoxicity because it is not conserved within the APOL family and is dispensable for cell death in vitro. We discuss two models for APOL1 trypanolytic activity: one involving lysosome permeabilization and another involving colloidosmotic swelling of the cell body, as well as their relevance to human pathophysiology. Experimental evidence from human cell culture models suggests that both mechanisms may be operative. A systems biology approach whereby APOL1-associated perturbations in gene and protein expression in affected individuals are correlated with molecular pathways may be productive to elucidate APOL1 function in vivo. Published by Elsevier Inc.
引用
收藏
页码:222 / 236
页数:15
相关论文
共 50 条
  • [41] A focus on the association of Apol1 with kidney disease in children
    Ekulu, Pepe M.
    Nkoy, Agathe B.
    Adebayo, Oyindamola C.
    Kazadi, Orly K.
    Aloni, Michel N.
    Arcolino, Fanny O.
    Ngiyulu, Rene M.
    Gini, Jean-Lambert E.
    Lepira, Francois B.
    van den Heuvel, Lamberthus P.
    Levtchenko, Elena N.
    PEDIATRIC NEPHROLOGY, 2021, 36 (04) : 777 - 788
  • [42] APOL1 risk variants in kidney transplantation: a modulation of immune cell function
    Malone, Andrew F.
    JOURNAL OF CLINICAL INVESTIGATION, 2021, 131 (22)
  • [43] APOL1 Dynamics in Diabetic Kidney Disease and Hypertension
    Singhal, Pravin C.
    Skorecki, Karl
    BIOMOLECULES, 2025, 15 (02)
  • [44] APOL1 kidney disease risk variants cause cytotoxicity by depleting cellular potassium and inducing stress-activated protein kinases
    Olabisi, Opeyemi A.
    Zhang, Jia-Yue
    VerPlank, Lynn
    Zahler, Nathan
    DiBartolo, Salvatore, III
    Heneghan, John F.
    Schloendorff, Johannes S.
    Suh, Jung Hee
    Yan, Paul
    Alper, Seth L.
    Friedman, David J.
    Pollak, Martin R.
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (04) : 830 - 837
  • [45] The metabolic effects of APOL1 in humans
    Adeva-Andany, Maria M.
    Funcasta-Calderon, Raquel
    Fernandez-Fernandez, Carlos
    Ameneiros-Rodriguez, Eva
    Vila-Altesor, Matilde
    Castro-Quintela, Elvira
    PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2023, 475 (08): : 911 - 932
  • [46] APOL1 Risk Variants Associated with Serum Albumin in a Population-Based Cohort Study
    Chaudhary, Ninad S.
    Tiwari, Hemant K.
    Hidalgo, Bertha A.
    Limdi, Nita A.
    Reynolds, Richard J.
    Cushman, Mary
    Zakai, Neil A.
    Lange, Leslie
    Judd, Suzanne E.
    Winkler, Cheryl A.
    Kopp, Jeffrey B.
    Gutierrez, Orlando M.
    Irvin, Marguerite R.
    AMERICAN JOURNAL OF NEPHROLOGY, 2022, 53 (2-3) : 182 - 190
  • [47] APOL1 Nephropathy Risk Variant Associations with Diseases beyond the Kidney: APOL1 and Sepsis
    Ma, Lijun
    Freedman, Barry I.
    CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2019, 14 (12): : 1684 - 1686
  • [48] Intracellular APOL1 Risk Variants Cause Cytotoxicity Accompanied by Energy Depletion
    Granado, Daniel
    Mueller, Daria
    Krausel, Vanessa
    Kruzel-Davila, Etty
    Schuberth, Christian
    Eschborn, Melanie
    Wedlich-Soeldner, Roland
    Skorecki, Karl
    Pavenstaedt, Hermann
    Michgehl, Ulf
    Weide, Thomas
    JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2017, 28 (11): : 3226 - 3237
  • [49] APOL1 Genotype, Kidney and Cardiovascular Disease, and Death in Older Adults
    Mukamal, Kenneth J.
    Tremaglio, Joseph
    Friedman, David J.
    Ix, Joachim H.
    Kuller, Lewis H.
    Tracy, Russell P.
    Pollak, Martin R.
    ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2016, 36 (02) : 398 - 403
  • [50] Recessive, gain-of-function toxicity in an APOL1 BAC transgenic mouse model mirrors human APOL1 kidney disease
    McCarthy, Gizelle M.
    Blasio, Angelo
    Donovan, Olivia G.
    Schaller, Lena B.
    Bock-Hughes, Althea
    Magraner, Jose M.
    Suh, Jung Hee
    Tattersfield, Calum F.
    Stillman, Isaac E.
    Shah, Shrijal S.
    Zsengeller, Zsuzsanna K.
    Subramanian, Balajikarthick
    Friedman, David J.
    Pollak, Martin R.
    DISEASE MODELS & MECHANISMS, 2021, 14 (08)