title: ApoL1 and the Immune Response of Patients with Systemic Lupus Erythematosus.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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. We contend that alterations in crucial APOL1 intracellular pathways may underpin associated disease states based on structure-functional differences between variant and ancestral forms. While ancestral APOL1 may be a key driver of autophagy, nonconserved primary structure changes result in a toxic gain of function with attenuation of autophagy and an unsupervised pore-forming feature. Thus, the divergent intracellular biological pathways of ancestral and variant APOL1 may explain a worsened prognosis as demonstrated in SLE.
authors.affiliation: Division of Rheumatology, Department of Medicine, New York University School of Medicine, 550 First Avenue, MSB 611, New York, NY, 10016, USA. ashira.blazer@nyumc.org.
authors.forename: Ashira D
authors.initials: AD
authors.lastname: Blazer
authors.affiliation: Division of Rheumatology, Department of Medicine, New York University School of Medicine, 550 First Avenue, MSB 611, New York, NY, 10016, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Clancy
mesh_terms: D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics* / Q000502:physiology; D001343:Autophagy / Q000235:genetics; D002318:Cardiovascular Diseases / Q000235:genetics / Q000276:immunology; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008075:Lipoproteins, HDL / Q000235:genetics* / Q000502:physiology; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology*; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: Autoimmunity; Autophagy; Functional genetics