Gene–Gene and Gene–Environment Interactions in Apolipoprotein L1 Gene-Associated Nephropathy
Barry I. Freedman,Karl Skorecki +1 more
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TLDR
This work reviews the evidence supporting second hits or modifying factors that affect risk for apolipoprotein L1 gene-associated nephropathy and produce the protean manifestations of this common and complex syndrome.Abstract:
Molecular genetics have revolutionized the understanding of susceptibility to the broad spectrum of kidney diseases with light microscopic appearance of FSGS, particularly in populations with recent African ancestry. These disorders include idiopathic FSGS, HIV-associated nephropathy, severe lupus nephritis, sickle cell nephropathy, and the primary kidney disorder focal global glomerulosclerosis, which had historically been ascribed to systemic hypertension. FSGS was once thought to include a multitude of unrelated disorders with similar histologic appearance. However, variation in the apolipoprotein L1 gene locus is now known to account for the vast majority of such cases in African Americans as well as nearly all the excess risk for FSGS and related forms of progressive nondiabetic nephropathy in populations with recent African ancestry, relative to European ancestry. Inheriting two coding apolipoprotein L1 gene nephropathy risk variants is necessary for susceptibility to CKD; however, these variants alone are insufficient to produce disease. This work reviews the evidence supporting second hits or modifying factors that affect risk for apolipoprotein L1 gene-associated nephropathy and produce the protean manifestations of this common and complex syndrome. Targeting modifiable second factors will lead to preventive therapies for slowing progression of nondiabetic nephropathy in many patients possessing two apolipoprotein L1 gene risk variants. This model of genetic risk coupled with modifiable second hits will serve as a paradigm applicable to patients with CKD of various etiologies as well as a host of other complex disorders.read more
Citations
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Cardiovascular Health in African Americans: A Scientific Statement From the American Heart Association
Mercedes R. Carnethon,Jia Pu,George Howard,Michelle A. Albert,Cheryl A.M. Anderson,Alain G. Bertoni,Mahasin S. Mujahid,Latha Palaniappan,Herman A. Taylor,Monte S. Willis,Clyde W. Yancy +10 more
TL;DR: The higher prevalence of traditional cardiovascular risk factors underlies the relatively earlier age of onset of cardiovascular diseases among African Americans and contributes directly to the notable disparities in stroke, heart failure, and peripheral artery disease among African American.
Journal ArticleDOI
APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South Africans
Alex N. Kasembeli,Raquel Duarte,Michèle Ramsay,Pulane Mosiane,Caroline Dickens,Therese Dix-Peek,Sophie Limou,Efe Sezgin,George W. Nelson,Agnes B. Fogo,Stewart Goetsch,Jeffrey B. Kopp,Cheryl A. Winkler,Saraladevi Naicker +13 more
TL;DR: The results indicate HIV-positive, antiretroviral therapy-naïve South-African blacks with two APOL1 risk alleles are at very high risk for developing HIV-associated nephropathy.
Journal ArticleDOI
Social Determinants of Racial Disparities in CKD
Jenna M. Norton,Marva Moxey-Mims,Paul W. Eggers,Andrew S. Narva,Robert A. Star,Paul L. Kimmel,Griffin P. Rodgers +6 more
TL;DR: Altering the social determinants of health, although difficult, may embody important policy and research efforts, with the ultimate goal of improving outcomes for patients with kidney diseases, and minimizing the disparities between groups.
Journal ArticleDOI
AKI and Collapsing Glomerulopathy Associated with COVID-19 and APOL 1 High-Risk Genotype.
Huijuan Wu,Huijuan Wu,Christopher P. Larsen,Cesar F. Hernandez-Arroyo,M. Mohamed,Tiffany Caza,Moh’d A. Sharshir,Asim Chughtai,Liping Xie,Juan M Gimenez,T. Sandow,Mark A Lusco,Haichun Yang,Ellen Acheampong,Ivy A. Rosales,Robert B. Colvin,Agnes B. Fogo,Juan Carlos Q. Velez,Juan Carlos Q. Velez +18 more
TL;DR: Collapsing glomerulopathy in black patients with COVID-19 was associated with high-risk APOL1 variants, suggesting a possible alternative mechanism: a "two-hit" combination of genetic predisposition and cytokine-mediated host response to SARS-CoV-2 infection.
Journal ArticleDOI
APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors.
Barry I. Freedman,Stephen O. Pastan,Ajay K. Israni,David P. Schladt,Bruce A. Julian,Michael D. Gautreaux,Vera Hauptfeld,Robert A. Bray,Howard Gebel,Allan D. Kirk,Robert S. Gaston,Jeffrey Rogers,Alan C. Farney,Giuseppe Orlando,Robert J. Stratta,Sumit Mohan,Lijun Ma,Carl D. Langefeld,Donald W. Bowden,Pamela J. Hicks,Nicholette D. Palmer,Amudha Palanisamy,Amber Reeves-Daniel,W. Mark Brown,Jasmin Divers +24 more
TL;DR: Shorter renal allograft survival is reproducibly observed after deceased-donor kidney transplantation from APOL1 2-renal-risk-variant donors, and younger recipient age and older donor age have independent adverse effects on renal allogsraft survival.
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TL;DR: This article showed that focal segmental glomerulosclerosis (FSGS) and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22.
Association of Trypanolytic ApoL1 Variants with Kidney Disease in
Giulio Genovese,David J. Friedman,Michael W. Ross,Laurence Lecordier,Pierrick Uzureau,Barry I. Freedman,Donald W. Bowden,Carl D. Langefeld,Taras K. Oleksyk,Andrea L. Uscinski Knob,Andrea J. Bernhardy,Pamela J. Hicks,George W. Nelson,Benoit Vanhollebeke,Cheryl A. Winkler,Jeffrey B. Kopp,Etienne Pays,Martin R. Pollak +17 more
TL;DR: In African Americans, focal segmental glomerulosclerosis and hypertension-attributed end-stage kidney disease (H-ESKD) are associated with two independent sequence variants in the APOL1 gene on chromosome 22, which speculate that evolution of a critical survival factor in Africa may have contributed to the high rates of renal disease in African Americans.
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