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https://www.readbyqxmd.com/read/28924146/apols-with-low-ph-dependence-can-kill-all-african-trypanosomes
#1
Frédéric Fontaine, Laurence Lecordier, Gilles Vanwalleghem, Pierrick Uzureau, Nick Van Reet, Martina Fontaine, Patricia Tebabi, Benoit Vanhollebeke, Philippe Büscher, David Pérez-Morga, Etienne Pays
The primate-specific serum protein apolipoprotein L1 (APOL1) is the only secreted member of a family of cell death promoting proteins (1-4) . APOL1 kills the bloodstream parasite Trypanosoma brucei brucei, but not the human sleeping sickness agents T.b. rhodesiense and T.b. gambiense (3) . We considered the possibility that intracellular members of the APOL1 family, against which extracellular trypanosomes could not have evolved resistance, could kill pathogenic T. brucei subspecies. Here we show that recombinant APOL3 (rAPOL3) kills all African trypanosomes, including T...
September 18, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28918394/apolipoprotein-l1-confers-ph-switchable-ion-permeability-to-phospholipid-vesicles
#2
Jonathan Bruno, Nicola Pozzi, Jonathan Oliva, John C Edwards
Apolipoprotein L1 (ApoL1) is a human serum protein conferring resistance to African trypanosomes, and certain ApoL1 variants increase susceptibility to some progressive kidney diseases. ApoL1 has been hypothesized to function like a pore-forming colicin and been reported to have permeability effects on both intracellular and plasma membranes. Here, to gain insight into how ApoL1 may function in vivo, we used vesicle-based ion-permeability, direct membrane-association, and intrinsic fluorescence to study the activities of purified recombinant ApoL1...
September 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28852479/collapsing-glomerulopathy-a-30-year-perspective-and-single-large-center-experience
#3
L Nicholas Cossey, Christopher P Larsen, Helen Liapis
Collapsing glomerulopathy (CGP) is a pattern of kidney injury seen on renal biopsy with multiple associations and etiologies. It is most commonly described in African-Americans and others with recent African ancestry. The disease is rapidly progressive and often presents with abrupt onset of renal failure and nephrotic-range proteinuria. Since its description 30 years ago, this entity has transformed from a morphologic diagnosis typically seen in the setting of HIV infection to a complicated diagnosis with numerous etiologies, many of which are associated with underlying apolipoprotein L1 (APOL1)-risk variants or other genetic disorders...
August 2017: Clinical Kidney Journal
https://www.readbyqxmd.com/read/28845468/evolutionary-nephrology
#4
Robert L Chevalier
Progressive kidney disease follows nephron loss, hyperfiltration, and incomplete repair, a process described as "maladaptive." In the past 20 years, a new discipline has emerged that expands research horizons: evolutionary medicine. In contrast to physiologic (homeostatic) adaptation, evolutionary adaptation is the result of reproductive success that reflects natural selection. Evolutionary explanations for physiologically maladaptive responses can emerge from mismatch of the phenotype with environment or evolutionary tradeoffs...
May 2017: KI Reports
https://www.readbyqxmd.com/read/28842513/transcription-and-translation-of-apol1-variants-commentary
#5
Samina Ejaz
It is highly significant to document molecular alterations existing in the normal cells prior to the onset of any disease. Knowledge of genetic mutations and associated molecular mechanisms will be helpful for better diagnosis and management of diseases. Major focus of this commentary is to provide a comprehensive understanding about apolipoprotein 1 gene (APOL1), protein encoded by this gene (apoL1) and mechanistic details regarding role of apoL1 in the lysis of Trypanosoma brucei Information about APOL1 genetic variants, APOL1G1 and APOL1G2, is provided along with the association of these variants with hypertension-attributed end-stage renal disease (ESRD) and focal segmental glomerulosclerosis (FSGS)...
August 25, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28835482/apol1-and-cardiovascular-disease-a-story-in-evolution
#6
EDITORIAL
Archna Bajaj, Katalin Susztak, Scott M Damrauer
No abstract text is available yet for this article.
September 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28827791/candidate-gene-polymorphisms-study-between-human-african-trypanosomiasis-clinical-phenotypes-in-guinea
#7
Justin Windingoudi Kaboré, Hamidou Ilboudo, Harry Noyes, Oumou Camara, Jacques Kaboré, Mamadou Camara, Mathurin Koffi, Veerle Lejon, Vincent Jamonneau, Annette MacLeod, Christiane Hertz-Fowler, Adrien Marie Gaston Belem, Enock Matovu, Bruno Bucheton, Issa Sidibe
BACKGROUND: Human African trypanosomiasis (HAT), a lethal disease induced by Trypanosoma brucei gambiense, has a range of clinical outcomes in its human host in West Africa: an acute form progressing rapidly to second stage, spontaneous self-cure and individuals able to regulate parasitaemia at very low levels, have all been reported from endemic foci. In order to test if this clinical diversity is influenced by host genetic determinants, the association between candidate gene polymorphisms and HAT outcome was investigated in populations from HAT active foci in Guinea...
August 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28801123/a-new-mouse-model-of-apol1-associated-kidney-diseases-when-traffic-gets-snarled-the-podocyte-suffers
#8
EDITORIAL
John F O'Toole, Leslie A Bruggeman, John R Sedor
No abstract text is available yet for this article.
August 9, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28800731/the-analysis-of-apol1-genetic-variation-and-haplotype-diversity-provided-by-1000-genomes-project
#9
Ting Peng, Li Wang, Guisen Li
BACKGROUND: The APOL1 gene variants has been shown to be associated with an increased risk of multiple kinds of diseases, particularly in African Americans, but not in Caucasians and Asians. In this study, we explored the single nucleotide polymorphism (SNP) and haplotype diversity of APOL1 gene in different races provided by 1000 Genomes project. METHODS: Variants of APOL1 gene in 1000 Genome Project were obtained and SNPs located in the regulatory region or coding region were selected for genetic variation analysis...
August 11, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28771472/micrornas-in-the-mir-17-and-mir-15-families-are-downregulated-in-chronic-kidney-disease-with-hypertension
#10
Priyanka Nandakumar, Adrienne Tin, Megan L Grove, Jianzhong Ma, Eric Boerwinkle, Josef Coresh, Aravinda Chakravarti
BACKGROUND: In older adults (aged 70-74 years), African-Americans have 4-fold higher risk of developing hypertension-attributed end-stage renal disease (ESRD) than European-Americans. A hypothesized mechanism linking hypertension and progressive chronic kidney disease (CKD) is the innate immune response and inflammation. Persons with CKD are also more susceptible to infection. Gene expression in peripheral blood can provide a view of the innate immune activation profile. We aimed to identify differentially expressed genes, microRNAs, and pathways in peripheral blood between cases with CKD and high blood pressure under hypertension treatment versus controls without CKD and with controlled blood pressure in African Americans...
2017: PloS One
https://www.readbyqxmd.com/read/28758155/apol1-renal-risk-variants-do-not-associate-with-incident-cardiovascular-disease-or-mortality-in-the-systolic-blood-pressure-intervention-trial
#11
Barry I Freedman, Michael V Rocco, Jeffrey T Bates, Michel Chonchol, Amret T Hawfield, James P Lash, Vasilios Papademetriou, John R Sedor, Karen Servilla, Paul L Kimmel, Barry M Wall, Nicholas M Pajewski
INTRODUCTION: Relationships between apolipoprotein L1 gene (APOL1) renal-risk variants (RRVs) and cardiovascular disease (CVD) remain controversial. To clarify associations between APOL1 and CVD, 2,568 African American Systolic Blood Pressure Intervention Trial (SPRINT) participants were assessed for the incidence of CVD events (primary composite including non-fatal myocardial infarction, acute coronary syndrome not resulting in myocardial infarction, nonfatal stroke, non-fatal acute decompensated heart failure, and CVD death), renal outcomes, and all-cause mortality...
July 2017: KI Reports
https://www.readbyqxmd.com/read/28732083/apol1-risk-alleles-among-individuals-with-ckd-in-northern-tanzania-a-pilot-study
#12
John W Stanifer, Francis Karia, Venance Maro, Kajiru Kilonzo, Xuejun Qin, Uptal D Patel, Elizabeth R Hauser
INTRODUCTION: In sub-Saharan Africa, approximately 100 million people have CKD, yet genetic risk factors are not well-understood. Despite the potential importance of understanding APOL1 risk allele status among individuals with CKD, little genetic research has been conducted. Therefore, we conducted a pilot study evaluating the feasibility of and willingness to participate in genetic research on kidney disease, and we estimated APOL1 risk allele frequencies among individuals with CKD...
2017: PloS One
https://www.readbyqxmd.com/read/28724794/apol1-variants-change-c-terminal-conformational-dynamics-and-binding-to-snare-protein-vamp8
#13
Sethu M Madhavan, John F O'Toole, Martha Konieczkowski, Laura Barisoni, David B Thomas, Santhi Ganesan, Leslie A Bruggeman, Matthias Buck, John R Sedor
APOL1 variants in African populations mediate resistance to trypanosomal infection but increase risk for kidney diseases through unknown mechanisms. APOL1 is expressed in glomerular podocytes and does not vary with underlying kidney disease diagnoses or APOL1 genotypes, suggesting that the kidney disease-associated variants dysregulate its function rather than its localization or abundance. Structural homology searches identified vesicle-associated membrane protein 8 (VAMP8) as an APOL1 protein interactor. VAMP8 colocalizes with APOL1 in the podocyte, and the APOL1:VAMP8 interaction was confirmed biochemically and with surface plasmon resonance...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28699644/roles-of-apol1%C3%A2-g1-and-g2-variants-in-sickle-cell-disease-patients-kidney-is-the-main-target
#14
Raphaël Kormann, Anne-Sophie Jannot, Céline Narjoz, Jean-Antoine Ribeil, Sandra Manceau, Marianne Delville, Valentin Joste, Dominique Prié, Jacques Pouchot, Eric Thervet, Marie Courbebaisse, Jean-Benoît Arlet
In African-American patients with sickle cell disease (SCD), APOL1 G1 and G2 variants are associated with increased risk of sickle cell nephropathy (SCN). To determine the role of APOL1 variants in SCD patients living in Europe, we genotyped 152 SCD patients [aged 30·4 (24·3-36·4) years], mainly of Sub-Saharan African ancestry, for APOL1 G1 and G2 and for variants of four genes with kidney tropism (GSTM1, GSTT1, GSTP1, and HMOX1). Homozygous or double-heterozygous APOL G1 and G2 genotypes were strongly associated with end stage renal disease (P = 0·003) and worse Kidney Disease: Improving Global Outcomes stages (P = 0·001)...
July 12, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28696248/intracellular-apol1-risk-variants-cause-cytotoxicity-accompanied-by-energy-depletion
#15
Daniel Granado, Daria Müller, Vanessa Krausel, Etty Kruzel-Davila, Christian Schuberth, Melanie Eschborn, Roland Wedlich-Söldner, Karl Skorecki, Hermann Pavenstädt, Ulf Michgehl, Thomas Weide
Population genetic approaches have uncovered a strong association between kidney diseases and two sequence variants of the APOL1 gene, called APOL1 risk variant G1 and variant G2, compared with the nonrisk G0 allele. However, the mechanism whereby these variants lead to disease manifestation and, in particular, whether this involves an intracellular or extracellular pool of APOL1 remains unclear. Herein, we show a predominantly intracellular localization of APOL1 G0 and the renal risk variants, which localized to membranes of the endoplasmic reticulum in podocyte cell lines...
July 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28669990/chronic-kidney-disease-role-of-supar-in-apol1-associated-kidney-disease
#16
Ellen F Carney
No abstract text is available yet for this article.
September 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28650456/a-tripartite-complex-of-supar-apol1-risk-variants-and-%C3%AE-v%C3%AE-3-integrin-on-podocytes-mediates-chronic-kidney-disease
#17
Salim S Hayek, Kwi Hye Koh, Morgan E Grams, Changli Wei, Yi-An Ko, Jing Li, Beata Samelko, Hyun Lee, Ranadheer R Dande, Ha Won Lee, Eunsil Hahm, Vasil Peev, Melissa Tracy, Nicholas J Tardi, Vineet Gupta, Mehmet M Altintas, Garrett Garborcauskas, Nikolina Stojanovic, Cheryl A Winkler, Michael S Lipkowitz, Adrienne Tin, Lesley A Inker, Andrew S Levey, Martin Zeier, Barry I Freedman, Jeffrey B Kopp, Karl Skorecki, Josef Coresh, Arshed A Quyyumi, Sanja Sever, Jochen Reiser
Soluble urokinase plasminogen activator receptor (suPAR) independently predicts chronic kidney disease (CKD) incidence and progression. Apolipoprotein L1 (APOL1) gene variants G1 and G2, but not the reference allele (G0), are associated with an increased risk of CKD in individuals of recent African ancestry. Here we show in two large, unrelated cohorts that decline in kidney function associated with APOL1 risk variants was dependent on plasma suPAR levels: APOL1-related risk was attenuated in patients with lower suPAR, and strengthened in those with higher suPAR levels...
August 2017: Nature Medicine
https://www.readbyqxmd.com/read/28611783/apolipoprotein-l1-genetic-variants-are-associated-with-chronic-kidney-disease-but-not-with-cardiovascular-disease-in-a-population-referred-for-cardiac-catheterization
#18
Hanghang Wang, Patrick H Pun, Lydia Kwee, Damian Craig, Carol Haynes, Megan Chryst-Ladd, Laura P Svetkey, Uptal D Patel, Elizabeth R Hauser, Martin R Pollak, William E Kraus, Svati H Shah
BACKGROUND: While the association between APOL1 genetic variants and chronic kidney disease (CKD) has been established, their association with cardiovascular disease (CVD) is unclear. This study sought to understand CKD and cardiovascular risk conferred by APOL1 variants in a secondary cardiovascular prevention population. METHODS: Two risk variants in APOL1 were genotyped in African-Americans (n = 1,641) enrolled in the CATHGEN biorepository, comprised of patients referred for cardiac catheterization at Duke University Hospital, Durham, NC, USA (2001-2010)...
February 2017: Cardiorenal Medicine
https://www.readbyqxmd.com/read/28578979/hiv-associated-kidney-diseases-clarifying-concordance-between-renal-failure-in-hiv-infection-and-histopathologic-manifestations-at-kidney-biopsy
#19
REVIEW
Carla L Ellis
Patients with HIV infection have a wide spectrum of renal diseases. Some are known to be the direct effect of the viral infection while others are renal diseases that also occur in uninfected populations. HIV associated nephropathy (HIVAN) is considered to be a subtype of primary focal and segmental glomerulosclerosis that is distinct in HIV infected patients. It is more frequent in the African-American population and associated with mutations of the apolipoprotein L1 (APOL1) gene. HIV associated immune complex kidney disease (HIVICD) encompasses a spectrum of HIV associated renal diseases characterized by the presence of immune complex deposition within glomeruli...
July 2017: Seminars in Diagnostic Pathology
https://www.readbyqxmd.com/read/28572159/apol1-risk-variants-and-cardiovascular-disease-results-from-the-aask-african-american-study-of-kidney-disease-and-hypertension
#20
RANDOMIZED CONTROLLED TRIAL
Teresa K Chen, Lawrence J Appel, Morgan E Grams, Adrienne Tin, Michael J Choi, Michael S Lipkowitz, Cheryl A Winkler, Michelle M Estrella
OBJECTIVE: Among African Americans, the apolipoprotein L1 (APOL1) risk variants have been associated with various types of kidney disease and chronic kidney disease progression. We aimed to determine whether these same risk variants also confer an increased risk for cardiovascular disease. APPROACH AND RESULTS: In a cohort of African Americans with hypertension-attributed chronic kidney disease followed for up to 12 years, we used Cox proportional hazards models to estimate the relative hazard of a composite cardiovascular disease outcome (cardiovascular death or hospitalization for myocardial infarction, cardiac revascularization procedure, heart failure, or stroke) for the APOL1 high- (2 risk variants) versus low-risk (0-1 risk variant) genotypes...
September 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
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