title: JC polyoma virus interacts with APOL1 in African Americans with nondiabetic nephropathy.
abstract: Individuals with HIV infection and two apolipoprotein L1 gene (APOL1) risk variants frequently develop nephropathy. Here we tested whether non-HIV viral infections influence nephropathy risk via interactions with APOL1 by assessing APOL1 genotypes and presence of urine JC and BK polyoma virus and plasma HHV6 and CMV by quantitative polymerase chain reaction. We analyzed 300 samples from unrelated and related first-degree relatives of African Americans with nondiabetic nephropathy using linear and nonlinear mixed models to account for familial relationships. The four groups evaluated were APOL1 zero/one versus two risk alleles, with or without nephropathy. Urine JCV and BKV were detected in 90 and 29 patients, respectively, whereas HHV6 and CMV were rare. Adjusting for family age at nephropathy, gender, and ancestry, presence of JCV genomic DNA in urine and APOL1 risk alleles were significantly negatively associated with elevated serum cystatin C, albuminuria (albumin-to-creatinine ratio over 30 mg/g), and kidney disease defined as an eGFR under 60 ml/min per 1.73 m(2) and/or albuminuria in an additive (APOL1 plus JCV) model. BK viruria was not associated with kidney disease. Thus, African Americans at increased risk for APOL1-associated nephropathy (two APOL1 risk variants) with JC viruria had a lower prevalence of kidney disease, suggesting that JCV interaction with APOL1 genotype may influence kidney disease risk.
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Divers
authors.forename: Marina
authors.initials: M
authors.lastname: Núñez
authors.forename: Kevin P
authors.initials: KP
authors.lastname: High
authors.forename: Mariana
authors.initials: M
authors.lastname: Murea
authors.forename: Michael V
authors.initials: MV
authors.lastname: Rocco
authors.forename: Lijun
authors.initials: L
authors.lastname: Ma
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Hicks
authors.forename: Mitzie
authors.initials: M
authors.lastname: Spainhour
authors.forename: David A
authors.initials: DA
authors.lastname: Ornelles
authors.forename: Steven B
authors.initials: SB
authors.lastname: Kleiboeker
authors.forename: Kara
authors.initials: K
authors.lastname: Duncan
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Jolyn
authors.initials: J
authors.lastname: Turner
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000419:Albuminuria / Q000208:ethnology / Q000235:genetics / Q000821:virology; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics*; D016009:Chi-Square Distribution; D055316:Cystatin C / Q000097:blood; D004279:DNA, Viral / Q000652:urine; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000302:isolation & purification*; D007674:Kidney Diseases / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology / Q000517:prevention & control / Q000821:virology*; D016014:Linear Models; D008075:Lipoproteins, HDL / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017711:Nonlinear Dynamics; D009657:North Carolina / Q000453:epidemiology; D010641:Phenotype; D027601:Polyomavirus Infections / Q000208:ethnology / Q000821:virology*; D015995:Prevalence; D012307:Risk Factors; D014412:Tumor Virus Infections / Q000208:ethnology / Q000821:virology*
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; C525030:CST3 protein, human; D055316:Cystatin C; D004279:DNA, Viral; D008075:Lipoproteins, HDL