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APOL1

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https://www.readbyqxmd.com/read/28339911/a-null-variant-in-the-apolipoprotein-l3-gene-is-associated-with-non-diabetic-nephropathy
#1
Karl L Skorecki, Jessica H Lee, Carl D Langefeld, Saharon Rosset, Shay Tzur, Walter G Wasser, Revital Shemer, Gregory A Hawkins, Jasmin Divers, Rulan S Parekh, Man Li, Matthew G Sampson, Matthias Kretzler, Martin R Pollak, Shrijal Shah, Daniel Blackler, Brendan Nichols, Michael Wilmot, Seth L Alper, Barry I Freedman, David J Friedman
Background.: Inheritance of apolipoprotein L1 gene ( APOL1 ) renal-risk variants in a recessive pattern strongly associates with non-diabetic end-stage kidney disease (ESKD). Further evidence supports risk modifiers in APOL1 -associated nephropathy; some studies demonstrate that heterozygotes possess excess risk for ESKD or show earlier age at ESKD, relative to those with zero risk alleles. Nearby loci are also associated with ESKD in non-African Americans. Methods.: We assessed the role of the APOL3 null allele rs11089781 on risk of non-diabetic ESKD...
February 20, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28335839/apolipoprotein-l1-variants%C3%A2-and-blood-pressure-traits-in%C3%A2-african-americans
#2
Girish N Nadkarni, Geneviève Galarneau, Stephen B Ellis, Rajiv Nadukuru, Jinglan Zhang, Stuart A Scott, Claudia Schurmann, Rongling Li, Laura J Rasmussen-Torvik, Abel N Kho, M Geoffrey Hayes, Jennifer A Pacheco, Teri A Manolio, Rex L Chisholm, Dan M Roden, Joshua C Denny, Eimear E Kenny, Erwin P Bottinger
BACKGROUND: African Americans (AA) are disproportionately affected by hypertension-related health disparities. Apolipoprotein L1 (APOL1) risk variants are associated with kidney disease in hypertensive AAs. OBJECTIVES: This study assessed the APOL1 risk alleles' association with blood pressure traits in AAs. METHODS: The discovery cohort included 5,204 AA participants from Mount Sinai's BioMe biobank. Replication cohorts included additional BioMe (n = 1,623), Vanderbilt BioVU (n = 1,809), and Northwestern NUgene (n = 567) AA biobank participants...
March 28, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28314574/apol1-a-case-in-point-for-replacing-race-with-genetics
#3
Girish N Nadkarni, Christina M Wyatt, Barbara Murphy, Michael J Ross
Ethnicity-specific differences in apolipoprotein L1 (APOL1) polymorphisms are associated with racial disparities in kidney transplantation outcomes. APOL1 genotyping may better help define graft outcome risk pre-transplantation; however, more research is needed.
April 2017: Kidney International
https://www.readbyqxmd.com/read/28298955/the-apolipoprotein-l1-gene-and-cardiovascular-disease
#4
Todd W Robinson, Barry I Freedman
Relative to those with European ancestry, African Americans have an excess incidence of nondiabetic chronic kidney disease predominantly due to two coding renal-risk variants in the apolipoprotein L1 gene (APOL1). This APOL1-kidney disease association is independent of systemic hypertension or blood pressure. Recent reports describe extra-renal effects of the APOL1 G1 and G2 renal-risk variants on cardiovascular disease (CVD), subclinical atherosclerosis, lipoprotein particle concentrations, and survival. However, results have been less consistent than those seen in kidney disease, and the observed APOL1 associations with CVD vary from risk to protective...
October 2016: Methodist DeBakey Cardiovascular Journal
https://www.readbyqxmd.com/read/28280138/sickle-cell-trait-and-the-risk-of-esrd-in-blacks
#5
Rakhi P Naik, Marguerite R Irvin, Suzanne Judd, Orlando M Gutiérrez, Neil A Zakai, Vimal K Derebail, Carmen Peralta, Michael R Lewis, Degui Zhi, Donna Arnett, William McClellan, James G Wilson, Alexander P Reiner, Jeffrey B Kopp, Cheryl A Winkler, Mary Cushman
Blacks, compared with whites, have an increased risk of progression to end-stage renal disease (ESRD). Emerging evidence suggests that, in addition to APOL1 high-risk genotypes, hemoglobin variants, including sickle cell trait (SCT) and hemoglobin C trait, have a role in kidney disease in blacks. However, the association between these hemoglobin traits and ESRD remains unknown. In a large population-based cohort, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we evaluated 9909 self-reported blacks (739 with SCT and 243 with hemoglobin C trait)...
March 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28265848/apol1-and-the-immune-response-of-patients-with-systemic-lupus-erythematosus
#6
REVIEW
Ashira D Blazer, Robert M Clancy
PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) confers up to a 50-fold increased risk of cardiovascular disease (CVD), and African Americans with SLE experience accelerated damage accrual and doubled cardiovascular risk when compared to their European American counterparts. RECENT FINDINGS: Genome-wide association studies have identified a substantial signal at 22q13, now assigned to variation at apolipoprotein L1 (APOL1), which has associated with progressive nondiabetic nephropathy, cardiovascular disease, and many immune-associated renal diseases, including lupus nephritis...
March 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28262774/genetics-apol1-risk-variants-drive-kidney-disease-in-mice
#7
Susan J Allison
No abstract text is available yet for this article.
March 6, 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28242845/focal-segmental-glomerulosclerosis
#8
Avi Z Rosenberg, Jeffrey B Kopp
Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant-important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS...
March 7, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28238999/race-genomics-and-chronic-disease-what-patients-with-african-ancestry-have-to-say
#9
Carol R Horowitz, Kadija Ferryman, Rennie Negron, Tatiana Sabin, Mayra Rodriguez, Randi F Zinberg, Erwin Böttinger, Mimsie Robinson
BACKGROUND: Variants of the APOL1 gene increase risk for kidney failure 10-fold, and are nearly exclusively found in people with African ancestry. To translate genomic discoveries into practice, we gathered information about effects and challenges incorporating genetic risk in clinical care. METHODS: An academic-community-clinical team tested 26 adults with self-reported African ancestry for APOL1 variants, conducting in-depth interviews about patients' beliefs and attitudes toward genetic testing- before, immediately, and 30 days after receiving test results...
2017: Journal of Health Care for the Poor and Underserved
https://www.readbyqxmd.com/read/28218918/transgenic-expression-of-human-apol1-risk-variants-in-podocytes-induces-kidney-disease-in-mice
#10
Pazit Beckerman, Jing Bi-Karchin, Ae Seo Deok Park, Chengxiang Qiu, Patrick D Dummer, Irfana Soomro, Carine M Boustany-Kari, Steven S Pullen, Jeffrey H Miner, Chien-An A Hu, Tibor Rohacs, Kazunori Inoue, Shuta Ishibe, Moin A Saleem, Matthew B Palmer, Ana Maria Cuervo, Jeffrey B Kopp, Katalin Susztak
African Americans have a heightened risk of developing chronic and end-stage kidney disease, an association that is largely attributed to two common genetic variants, termed G1 and G2, in the APOL1 gene. Direct evidence demonstrating that these APOL1 risk alleles are pathogenic is still lacking because the APOL1 gene is present in only some primates and humans; thus it has been challenging to demonstrate experimental proof of causality of these risk alleles for renal disease. Here we generated mice with podocyte-specific inducible expression of the APOL1 reference allele (termed G0) or each of the risk-conferring alleles (G1 or G2)...
February 20, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28196842/identifying-the-intracellular-function-of-apol1
#11
EDITORIAL
Leslie A Bruggeman, John F O'Toole, John R Sedor
No abstract text is available yet for this article.
February 14, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28187045/apolipoprotein-l1-and-chronic-kidney-disease-risk-in-young-potential-living-kidney-donors
#12
Jayme E Locke, Deirdre Sawinski, Rhiannon D Reed, Brittany Shelton, Paul A MacLennan, Vineeta Kumar, Shikha Mehta, Roslyn B Mannon, Robert Gaston, Bruce A Julian, John J Carr, James G Terry, Meredith Kilgore, Allan B Massie, Dorry L Segev, Cora E Lewis
OBJECTIVE: The aim of this study was to develop a novel chronic kidney disease (CKD) risk prediction tool for young potential living kidney donors. SUMMARY OF BACKGROUND DATA: Living kidney donor selection practices have evolved from examining individual risk factors to a risk calculator incorporating multiple characteristics. Owing to limited long-term data and lack of genetic information, current risk tools lack precision among young potential living kidney donors, particularly African Americans (AAs)...
February 9, 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28143671/apol1-gene-kidney-risk-variants-and-cardiovascular-disease-getting-to-the-heart-of-the-matter
#13
REVIEW
Nicholas O McLean, Todd W Robinson, Barry I Freedman
Apolipoprotein L1 gene (APOL1) renal risk variants exhibit strong genetic associations with a spectrum of nondiabetic kidney diseases in individuals with recent African ancestry. Relationships between APOL1 kidney risk variants and cardiovascular disease (CVD) susceptibility and CVD-related death remain controversial. Some studies detected an increased risk for CVD, whereas others support protection from death and subclinical CVD and cerebrovascular disease. Because treatments for nondiabetic kidney disease may target this gene and its protein products, it remains critical to clarify the potential extrarenal effects of APOL1 kidney risk variants...
January 28, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28100445/apol1-variants-may-induce-hiv-associated-nephropathy-during-hiv-primary-infection
#14
Marine De Laroche, Geoffroy Desbuissons, Philippe Rouvier, Francis Barin, Gilbert Deray, Eric Caumes, Christine Katlama, Roland Tubiana, Corinne Isnard Bagnis
No abstract text is available yet for this article.
January 18, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28087008/apol1-genotype-blood-pressure-and-survival-in-african-americans-with-nondiabetic-nephropathy
#15
Todd W Robinson, Barry I Freedman
Several landmark trials have assessed the effects of aggressive hypertension control on the progression of nondiabetic chronic kidney disease. Results generally have been disappointing. With the realization that lowering blood pressure, including with renin-angiotensin system blockade, failed to reliably prevent end-stage kidney disease, studies now are analyzing longer-term effects of hypertension control on survival in chronic kidney disease. This commentary reviews the current findings and extends the discussion to apolipoprotein L1 gene by blood pressure (or gene by environment) interactions...
February 2017: Kidney International
https://www.readbyqxmd.com/read/28056107/autophagy-is-an-innate-mechanism-associated-with-leprosy-polarization
#16
Bruno Jorge de Andrade Silva, Mayara Garcia de Mattos Barbosa, Priscila Ribeiro Andrade, Helen Ferreira, José Augusto da Costa Nery, Suzana Côrte-Real, Gilberto Marcelo Sperandio da Silva, Patricia Sammarco Rosa, Mario Fabri, Euzenir Nunes Sarno, Roberta Olmo Pinheiro
Leprosy is a chronic infectious disease that may present different clinical forms according to the immune response of the host. Levels of IFN-γ are significantly raised in paucibacillary tuberculoid (T-lep) when compared with multibacillary lepromatous (L-lep) patients. IFN-γ primes macrophages for inflammatory activation and induces the autophagy antimicrobial mechanism. The involvement of autophagy in the immune response against Mycobacterium leprae remains unexplored. Here, we demonstrated by different autophagic assays that LC3-positive autophagosomes were predominantly observed in T-lep when compared with L-lep lesions and skin-derived macrophages...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/27932478/most-apol1-is-secreted-by-the-liver
#17
Khuloud Shukha, Jessica L Mueller, Raymond T Chung, Michael P Curry, David J Friedman, Martin R Pollak, Anders H Berg
Two coding sequence variants in the APOL1 gene (G1 and G2) explain much of the increased risk for FSGS, HIV-associated nephropathy, and hypertension-attributed ESRD among people of recent African ancestry. The ApoL1 protein is expressed in a wide variety of cell tissues. It has been assumed that the majority of circulating ApoL1 is produced by the liver, but this has not been shown. Using mass spectrometry, we genotyped and quantified the circulating ApoL1 in two liver transplant recipients whose native APOL1 genotype differed from the genotype of the deceased donors, allowing us to differentiate liver- from nonliver-produced ApoL1...
December 8, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27927600/strict-blood-pressure-control-associates-with-decreased-mortality-risk-by-apol1-genotype
#18
Elaine Ku, Michael S Lipkowitz, Lawrence J Appel, Afshin Parsa, Jennifer Gassman, David V Glidden, Miroslaw Smogorzewski, Chi-Yuan Hsu
Although APOL1 high-risk genotype partially accounts for the increased susceptibility of blacks to chronic kidney disease (CKD), whether APOL1 associates differentially with mortality risk remains controversial. Here we evaluate the association between APOL1 genotype and risk of death and determine whether APOL1 status modifies the association between strict versus usual blood pressure control and mortality risk. We performed a retrospective analysis of the African American Study of Kidney Disease and Hypertension trial that randomized black participants with CKD to strict versus usual blood pressure control from 1995 to 2001...
February 2017: Kidney International
https://www.readbyqxmd.com/read/27916972/chronic-kidney-disease-mechanisms-of-apol1-associated-renal-disease
#19
Ellen F Carney
No abstract text is available yet for this article.
February 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/27900314/renal-and-cardiovascular-morbidities-associated-with-apol1-status-among-african-american-and-non-african-american-children-with-focal-segmental-glomerulosclerosis
#20
Robert P Woroniecki, Derek K Ng, Sophie Limou, Cheryl A Winkler, Kimberly J Reidy, Mark Mitsnefes, Matthew G Sampson, Craig S Wong, Bradley A Warady, Susan L Furth, Jeffrey B Kopp, Frederick J Kaskel
BACKGROUND AND OBJECTIVES: African-American (AA) children with focal segmental glomerulosclerosis (FSGS) have later onset disease that progresses more rapidly than in non-AA children. It is unclear how APOL1 genotypes contribute to kidney disease risk, progression, and cardiovascular morbidity in children. DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: We examined the prevalence of APOL1 genotypes and associated cardiovascular phenotypes among children with FSGS in the Chronic Kidney Disease in Children (CKiD) study; an ongoing multicenter prospective cohort study of children aged 1-16 years with mild to moderate kidney disease...
2016: Frontiers in Pediatrics
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