title: Apolipoprotein L1 nephropathy risk variants associate with HDL subfraction concentration in African Americans.
abstract: BACKGROUND
  Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with non-diabetic nephropathy in African Americans. ApoL1 proteins associate with high-density lipoprotein (HDL) particles in the circulation. Plasma HDL particle subclass concentrations were compared in 73 African Americans based on APOL1 genotypes to detect differences potentially contributing to renal disease.
  
  
  METHODS
  HDL subclass concentrations were measured using nuclear magnetic resonance spectroscopy in African American first-degree relatives of patients with non-diabetic end-stage renal disease. Participants had estimated glomerular filtration rates (GFRs) > 80 mL/min and lacked albuminuria. Additive effects of the number of APOL1 risk variants on natural logarithm-transformed HDL subclass concentrations were computed.
  
  
  RESULTS
  Participants were 58.9% female with mean ± SD age 47.2 ± 13.3 years and GFR 92.4 ± 18.8 mL/min. The numbers with 2, 1 and 0 APOL1 nephropathy risk variants, respectively, were 36, 17 and 20. Mean ± SD medium-sized HDL concentrations were significantly lower for each additional APOL1 risk variant (2 versus 1 versus 0 risk variants: 9.0 ± 5.6 versus 10.1 ± 5.5 versus 13.1 ± 8.2 μmol/L, respectively; P = 0.0222 unadjusted; P = 0.0162 triglyceride- and ancestry adjusted).
  
  
  CONCLUSIONS
  Lower medium-sized HDL subclass concentrations are present in African Americans based on increasing numbers of APOL1 nephropathy risk variants. Potential mechanistic roles of altered medium HDL concentrations on APOL1-associated renal microvascular diseases should be evaluated.
authors.affiliation: Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA. bfreedma@wakehealth.edu
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Mariana
authors.initials: M
authors.lastname: Murea
authors.forename: Lijun
authors.initials: L
authors.lastname: Ma
authors.forename: James D
authors.initials: JD
authors.lastname: Otvos
authors.forename: Jolyn
authors.initials: J
authors.lastname: Turner
authors.forename: Peter A
authors.initials: PA
authors.lastname: Antinozzi
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hicks
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Michael V
authors.initials: MV
authors.lastname: Rocco
authors.forename: John S
authors.initials: JS
authors.lastname: Parks
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000209:etiology*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood / Q000208:ethnology* / Q000235:genetics*; D007677:Kidney Function Tests; D008075:Lipoproteins, HDL / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL