title: APOL1 nephropathy risk variants are associated with altered high-density lipoprotein profiles in African Americans.
abstract: Two independent coding variants in the apolipoprotein L1 gene (APOL1), G1 and G2, strongly associate with nephropathy in African Americans; associations with cardiovascular disease are more controversial. Although APOL1 binds plasma high-density lipoproteins (HDLs), data on APOL1 risk variant associations with HDL subfractions are sparse.
  
  
  
  Two APOL1 G1 single nucleotide polymorphisms and the G2 insertion/deletion polymorphism were genotyped in 2010 Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study participants with nuclear magnetic resonance spectroscopy-based lipoprotein subfraction measurements. Linear regression was used to model associations between numbers of APOL1 G1/G2 risk variants and HDL subfractions, adjusting for demographic, clinical and ancestral covariates.
  
  
  
  Female sex and higher percentage of African ancestry were positively associated with the number of APOL1 G1/G2 risk alleles. In the unadjusted analysis, mean (standard error) small HDL concentrations (μmol/L) for participants with zero, one and two G1/G2 risk alleles were 19.0 (0.2), 19.7 (0.2) and 19.9 (0.4), respectively (P = 0.02). Adjustment for age, sex, diabetes and African ancestry did not change the results but strengthened the statistical significance (P = 0.004). No significant differences in large or medium HDL, very low-density lipoprotein or low-density lipoprotein particle concentrations were observed by APOL1 genotype.
  
  
  
  Greater numbers of APOL1 G1/G2 risk alleles were associated with higher small HDL particle concentrations in African Americans. These results may suggest novel areas of investigation to uncover reasons for the association between APOL1 risk variants with adverse outcomes in African Americans.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Orlando M
authors.initials: OM
authors.lastname: Gutiérrez
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Judd
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Marguerite R
authors.initials: MR
authors.lastname: Irvin
authors.affiliation: Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Degui
authors.initials: D
authors.lastname: Zhi
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA.
authors.forename: Nita
authors.initials: N
authors.lastname: Limdi
authors.affiliation: Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, USA Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Nicholette D
authors.initials: ND
authors.lastname: Palmer
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.affiliation: Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA, USA.
authors.forename: Michèle M
authors.initials: MM
authors.lastname: Sale
authors.affiliation: Department of Internal Medicine-Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007674:Kidney Diseases / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000235:genetics / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL
keywords: APOL1; chronic kidney disease; ethnic disparities; genetics