Association of APOL1 variants with mild kidney disease in the first-degree relatives of African American patients with non-diabetic end-stage renal disease.
Familial aggregation of non-diabetic end-stage renal disease (ESRD) is found in African Americans and variants in the apolipoprotein L1 gene (APOL1) contribute to this risk. To detect genetic associations with milder forms of nephropathy in the high-risk families, analyses were performed using generalized estimating equations to assess relationships between kidney disease phenotypes and APOL1 variants in 786 relatives of 470 families. Adjusting for familial correlations, 23.1, 46.7, and 30.2% of genotyped relatives possessed two, one, or no APOL1 risk variants, respectively. Relatives with two compared with one or no risk variants had statistically indistinguishable median systolic blood pressure, urine albumin to creatinine ratio, estimated glomerular filtration rate (GFR; MDRD equation), and serum cystatin C levels. After adjusting for age, gender, age at ESRD in families, and African ancestry, significant associations were detected between APOL1 with overt proteinuria and estimated GFR (CKD-EPI equation), with a trend toward significance for quantitative albuminuria. Thus, relatives of African Americans with non-diabetic ESRD are enriched for APOL1 risk variants. After adjustment, two APOL1 risk variants weakly predict mild forms of kidney disease. Second hits appear necessary for the initiation of APOL1-associated nephropathy.
Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157-1053, USA. bfreedma@wakehealth.edu
Barry I
BI
Freedman
Carl D
CD
Langefeld
Jolyn
J
Turner
Marina
M
Núñez
Kevin P
KP
High
Mitzie
M
Spainhour
Pamela J
PJ
Hicks
Donald W
DW
Bowden
Amber M
AM
Reeves-Daniel
Mariana
M
Murea
Michael V
MV
Rocco
Jasmin
J
Divers
D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000208:ethnology / Q000235:genetics; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D044383:Black People / Q000235:genetics*; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005919:Glomerular Filtration Rate / Q000235:genetics; D040941:Heredity; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010375:Pedigree; D010641:Phenotype; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D055815:Young Adult; D001741:Black or African American
C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D008075:Lipoproteins, HDL