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APOL1

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https://www.readbyqxmd.com/read/28100445/apol1-variants-may-induce-hiv-associated-nephropathy-during-hiv-primary-infection
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
https://www.readbyqxmd.com/read/27864431/apol1-mediated-cell-injury-involves-disruption-of-conserved-trafficking-processes
#8
Etty Kruzel-Davila, Revital Shemer, Ayala Ofir, Ira Bavli-Kertselli, Ilona Darlyuk-Saadon, Pazit Oren-Giladi, Walter G Wasser, Daniella Magen, Eid Zaknoun, Maya Schuldiner, Adi Salzberg, Daniel Kornitzer, Zvonimir Marelja, Matias Simons, Karl Skorecki
APOL1 harbors C-terminal sequence variants (G1 and G2), which account for much of the increased risk for kidney disease in sub-Saharan African ancestry populations. Expression of the risk variants has also been shown to cause injury to podocytes and other cell types, but the underlying mechanisms are not understood. We used Drosophila melanogaster and Saccharomyces cerevisiae to help clarify these mechanisms. Ubiquitous expression of the human APOL1 G1 and G2 disease risk alleles caused near-complete lethality in D...
November 18, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27864430/apol1-g1-in-nephrocytes-induces-hypertrophy-and-accelerates-cell-death
#9
Yulong Fu, Jun-Yi Zhu, Adam Richman, Yi Zhang, Xuefang Xie, Jharna R Das, Jinliang Li, Patricio E Ray, Zhe Han
People of African ancestry carrying certain APOL1 mutant alleles are at elevated risk of developing renal diseases. However, the mechanisms underlying APOL1-associated renal diseases are unknown. Because the APOL1 gene is unique to humans and some primates, new animal models are needed to understand the function of APOL1 in vivo We generated transgenic Drosophila fly lines expressing the human APOL1 wild type allele (G0) or the predominant APOL1 risk allele (G1) in different tissues. Ubiquitous expression of APOL1 G0 or G1 in Drosophila induced lethal phenotypes, and G1 was more toxic than was G0...
November 18, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27862962/effect-of-replacing-race-with-apolipoprotein-l1-genotype-in-calculation-of-kidney-donor-risk-index
#10
B A Julian, R S Gaston, W M Brown, A M Reeves-Daniel, A K Israni, D P Schladt, S O Pastan, S Mohan, B I Freedman, J Divers
Renal allografts from deceased African Americans with two apolipoprotein L1 gene (APOL1) renal-risk variants fail sooner than kidneys from donors with fewer variants. Kidney Donor Risk Index (KDRI) was developed to evaluate organ offers by predicting allograft longevity and includes African American race as a risk factor. Substituting APOL1 genotype for race may refine the KDRI. For 622 deceased African American kidney donors, we applied 10-fold cross-validation approach to estimate contribution of APOL1 variants to a revised KDRI...
November 14, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27821631/apol1-renal-risk-variants-induce-mitochondrial-dysfunction
#11
Lijun Ma, Jeff W Chou, James A Snipes, Manish S Bharadwaj, Ann L Craddock, Dongmei Cheng, Allison Weckerle, Snezana Petrovic, Pamela J Hicks, Ashok K Hemal, Gregory A Hawkins, Lance D Miller, Anthony J A Molina, Carl D Langefeld, Mariana Murea, John S Parks, Barry I Freedman
APOL1 G1 and G2 variants facilitate kidney disease in blacks. To elucidate the pathways whereby these variants contribute to disease pathogenesis, we established HEK293 cell lines stably expressing doxycycline-inducible (Tet-on) reference APOL1 G0 or the G1 and G2 renal-risk variants, and used Illumina human HT-12 v4 arrays and Affymetrix HTA 2.0 arrays to generate global gene expression data with doxycycline induction. Significantly altered pathways identified through bioinformatics analyses involved mitochondrial function; results from immunoblotting, immunofluorescence, and functional assays validated these findings...
November 7, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27753822/pl-01-3-should-hypertension-treatment-targets-differ-according-to-region-and-ethnicity
#12
Lawrence Appel
With the exception of a few isolated populations, elevated blood pressure is a worldwide pandemic with staggering consequences for individuals, care givers, health care delivery systems, and insurers, including governments. It is well-recognized that the burden of hypertension and its adverse consequences is greater in low- and middle-income countries than economically developed countries. BP-related outcomes also differ by region, with a predominance of stroke in southeast Asian countries and a predominance of ischemic heart disease in the US and Western Europe...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27711207/genetic-modifiers-of-white-blood-cell-count-albuminuria-and-glomerular-filtration-rate-in-children-with-sickle-cell-anemia
#13
Beverly A Schaefer, Jonathan M Flanagan, Ofelia A Alvarez, Stephen C Nelson, Banu Aygun, Kerri A Nottage, Alex George, Carla W Roberts, Connie M Piccone, Thad A Howard, Barry R Davis, Russell E Ware
Discovery and validation of genetic variants that influence disease severity in children with sickle cell anemia (SCA) could lead to early identification of high-risk patients, better screening strategies, and intervention with targeted and preventive therapy. We hypothesized that newly identified genetic risk factors for the general African American population could also impact laboratory biomarkers known to contribute to the clinical disease expression of SCA, including variants influencing the white blood cell count and the development of albuminuria and abnormal glomerular filtration rate...
2016: PloS One
https://www.readbyqxmd.com/read/27658436/apol1-%C3%AE-thalassemia-and-bcl11a-variants-as-a-genetic-risk-profile-for-progression-of-chronic-kidney-disease-in-sickle-cell-anemia
#14
LETTER
Santosh L Saraf, Binal N Shah, Xu Zhang, Jin Han, Bamidele O Tayo, Taimur Abbasi, Adam Ostrower, Elizabeth Guzman, Robert E Molokie, Michel Gowhari, Johara Hassan, Shivi Jain, Richard S Cooper, Roberto F Machado, James P Lash, Victor R Gordeuk
No abstract text is available yet for this article.
January 2017: Haematologica
https://www.readbyqxmd.com/read/27650483/african-ancestry-specific-alleles-and-kidney-disease-risk-in-hispanics-latinos
#15
Holly J Kramer, Adrienne M Stilp, Cathy C Laurie, Alex P Reiner, James Lash, Martha L Daviglus, Sylvia E Rosas, Ana C Ricardo, Bamidele O Tayo, Michael F Flessner, Kathleen F Kerr, Carmen Peralta, Ramon Durazo-Arvizu, Matt Conomos, Timothy Thornton, Jerome Rotter, Kent D Taylor, Jainwen Cai, John Eckfeldt, Han Chen, George Papanicolau, Nora Franceschini
African ancestry alleles may contribute to CKD among Hispanics/Latinos, but whether associations differ by Hispanic/Latino background remains unknown. We examined the association of CKD measures with African ancestry-specific APOL1 alleles that were directly genotyped and sickle cell trait (hemoglobin subunit β gene [HBB] variant) on the basis of imputation in 12,226 adult Hispanics/Latinos grouped according to Caribbean or Mainland background. We also performed an unbiased genome-wide association scan of urine albumin-to-creatinine ratios...
September 20, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27644073/the-african-diaspora-history-adaptation-and-health
#16
REVIEW
Charles N Rotimi, Fasil Tekola-Ayele, Jennifer L Baker, Daniel Shriner
The trans-Atlantic slave trade brought millions of Africans to the New World. Advances in genomics are providing novel insights into the history and health of Africans and the diasporan populations. Recent examples reviewed here include the unraveling of substantial hunter-gatherer and 'Eurasian' admixtures across sub-Saharan Africa, expanding our understanding of ancestral African genetics; the global ubiquity of mixed ancestry; the revealing of African ancestry in Latin Americans that likely derived from the slave trade; and understanding of the ancestral backgrounds of APOL1 and LPL found to influence kidney disease and lipid levels, respectively, providing specific insights into disease etiology and health disparities...
December 2016: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/27642875/pl-01-3-should-hypertension-treatment-targets-differ-according-to-region-and-ethnicity
#17
Lawrence Appel
With the exception of a few isolated populations, elevated blood pressure is a worldwide pandemic with staggering consequences for individuals, care givers, health care delivery systems, and insurers, including governments. It is well-recognized that the burden of hypertension and its adverse consequences is greater in low- and middle-income countries than economically developed countries. BP-related outcomes also differ by region, with a predominance of stroke in southeast Asian countries and a predominance of ischemic heart disease in the US and Western Europe...
September 2016: Journal of Hypertension
https://www.readbyqxmd.com/read/27638911/an-investigation-of-apol1-risk-genotypes-and-preterm-birth-in-african-american-population-cohorts
#18
Catherine C Robertson, Christopher E Gillies, Rosemary K B Putler, Derek Ng, Kimberly J Reidy, Brendan Crawford, Matthew G Sampson
BACKGROUND: Two genetic variants in apolipoprotein L1 (APOL1) are associated with increased risk of focal segmental glomerulosclerosis as well as other glomerular phenotypes. These risk variants are common in individuals of African ancestry but absent in other racial groups. Yet, the majority of individuals with two APOL1 risk alleles [high-risk (HR) genotype] do not have renal disease. It is critical to identify environmental and secondary genetic influences that, when combined with these alleles, lead to kidney disease...
September 16, 2016: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/27610422/apol1-risk-alleles-are-associated-with-more-severe-arteriosclerosis-in-renal-resistance-vessels-with-aging-and-hypertension
#19
Michael D Hughson, Wendy E Hoy, Susan A Mott, Victor G Puelles, John F Bertram, Cheryl L Winkler, Jeffrey B Kopp
The increased risk of end-stage kidney disease (ESKD) among hypertensive African Americans is partly related to APOL1 allele variants. Hypertension-associated arterionephrosclerosis consists of arteriosclerosis, glomerulosclerosis, and cortical fibrosis. The initial glomerulosclerosis, attributed to preglomerular arteriosclerosis and ischemia, consists of focal global glomerulosclerosis (FGGS), but in biopsy studies, focal segmental glomerulosclerosis (FSGS) is found with progression to ESKD, particularly in African Americans...
May 2016: KI Reports
https://www.readbyqxmd.com/read/27600725/collapsing-glomerulopathy-in-a-young-woman-with-apol1-risk-alleles-following-acute-parvovirus-b19-infection-a-case-report-investigation
#20
Whitney Besse, Sherry Mansour, Karan Jatwani, Cynthia C Nast, Ursula C Brewster
BACKGROUND: Collapsing Glomerulopathy (CG), also known as the collapsing variant of Focal Segmental Glomerulosclerosis (FSGS), is distinct in both its clinical severity and its pathophysiologic characteristics from other forms of FSGS. This lesion occurs disproportionally in patients carrying two APOL1 risk alleles, and is the classic histologic lesion resulting from Human Immunodeficiency Virus (HIV) infection of podocytes. Other viral infections, including parvovirus B19, and drugs such as interferon that perturb the immune system, have also been associated with CG...
September 6, 2016: BMC Nephrology
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