title: Characterization of circulating APOL1 protein complexes in African Americans.
abstract: APOL1 gene renal-risk variants are associated with nephropathy and CVD in African Americans; however, little is known about the circulating APOL1 variant proteins which reportedly bind to HDL. We examined whether APOL1 G1 and G2 renal-risk variant serum concentrations or lipoprotein distributions differed from nonrisk G0 APOL1 in African Americans without nephropathy. Serum APOL1 protein concentrations were similar regardless of APOL1 genotype. In addition, serum APOL1 protein was bound to protein complexes in two nonoverlapping peaks, herein referred to as APOL1 complex A (12.2 nm diameter) and complex B (20.0 nm diameter). Neither of these protein complexes associated with HDL or LDL. Proteomic analysis revealed that complex A was composed of APOA1, haptoglobin-related protein (HPR), and complement C3, whereas complex B contained APOA1, HPR, IgM, and fibronectin. Serum HPR was less abundant on complex B in individuals with G1 and G2 renal-risk variant genotypes, relative to G0 (P = 0.0002-0.037). These circulating complexes may play roles in HDL metabolism and susceptibility to CVD.
authors.affiliation: Department of Internal Medicine, Sections on Molecular Medicine Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Allison
authors.initials: A
authors.lastname: Weckerle
authors.affiliation: Nephrology, Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: James A
authors.initials: JA
authors.lastname: Snipes
authors.affiliation: Department of Internal Medicine, Sections on Molecular Medicine Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Cheng
authors.affiliation: Department of Internal Medicine, Sections on Molecular Medicine Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Abraham K
authors.initials: AK
authors.lastname: Gebre
authors.affiliation: Department of Internal Medicine, Sections on Molecular Medicine Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Reisz
authors.affiliation: Nephrology, Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Mariana
authors.initials: M
authors.lastname: Murea
authors.affiliation: Department of Internal Medicine, Sections on Molecular Medicine Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Shelness
authors.affiliation: Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hawkins
authors.affiliation: Department of Internal Medicine, Sections on Molecular Medicine Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Furdui
authors.affiliation: Nephrology, Wake Forest School of Medicine, Winston-Salem, NC 27157.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.affiliation: Department of Internal Medicine, Sections on Molecular Medicine Wake Forest School of Medicine, Winston-Salem, NC 27157 jparks@wakehealth.edu lima@wakehealth.edu.
authors.forename: John S
authors.initials: JS
authors.lastname: Parks
authors.affiliation: Nephrology, Wake Forest School of Medicine, Winston-Salem, NC 27157 jparks@wakehealth.edu lima@wakehealth.edu.
authors.forename: Lijun
authors.initials: L
authors.lastname: Ma
mesh_terms: D000328:Adult; D001741:Black or African American; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000097:blood* / Q000235:genetics; D002318:Cardiovascular Diseases / Q000097:blood / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000235:genetics; D008075:Lipoproteins, HDL / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D012307:Risk Factors
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL
keywords: apolipoprotein L1; apolipoproteins; high density lipoprotein; kidney; proteomics; renal disease