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Brief Report: APOL1 Renal Risk Variants Are Associated With Chronic Kidney Disease in Children and Youth With Perinatal HIV Infection.

ABSTRACT: APOL1 renal risk alleles are associated with chronic kidney disease (CKD) in adults, with the strongest effect being for HIV-associated nephropathy. Their role in youth with perinatal HIV-1 infection (PHIV) has not been studied. In a nested case-control study of 451 PHIV participants in the Pediatric HIV/AIDS Cohort Study, we found a 3.5-fold increased odds of CKD in those carrying high-risk APOL1 genotypes using a recessive model [95% confidence interval (CI): 1.2 to 10.0]. We report an unadjusted incidence of 1.2 CKD cases/100 person-years (95% CI: 0.5 to 2.5) in PHIV youth carrying APOL1 high-risk genotypes, with important implications for sub-Saharan Africa.

SUBMITTER: Purswani MU

PROVIDER: S-EPMC4981510 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Brief Report: APOL1 Renal Risk Variants Are Associated With Chronic Kidney Disease in Children and Youth With Perinatal HIV Infection.

Purswani Murli U MU Patel Kunjal K Winkler Cheryl A CA Spector Stephen A SA Hazra Rohan R Seage George R GR Mofenson Lynne L Karalius Brad B Scott Gwendolyn B GB Van Dyke Russell B RB Kopp Jeffrey B JB

Journal of acquired immune deficiency syndromes (1999) 20160901 1

APOL1 renal risk alleles are associated with chronic kidney disease (CKD) in adults, with the strongest effect being for HIV-associated nephropathy. Their role in youth with perinatal HIV-1 infection (PHIV) has not been studied. In a nested case-control study of 451 PHIV participants in the Pediatric HIV/AIDS Cohort Study, we found a 3.5-fold increased odds of CKD in those carrying high-risk APOL1 genotypes using a recessive model [95% confidence interval (CI): 1.2 to 10.0]. We report an unadjus ...[more]

PMID: 27035887

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<i>APOL1</i> Renal Risk Variants and Kidney Function in HIV-1-Infected People From Sub-Saharan Africa.

Project description:IntroductionAPOL1 G1 and G2 alleles have been associated with kidney-related outcomes in people living with HIV (PLHIV) of Black African origin. No APOL1-related kidney risk data have yet been reported in PLHIV in West Africa, where high APOL1 allele frequencies have been observed.MethodsWe collected clinical data from PLHIV followed in Burkina Faso (N = 413) and in the ANRS-12169/2LADY trial (Cameroon, Senegal, Burkina Faso, N = 369). APOL1 G1 and G2 risk variants were genotyped using TaqMan assays, and APOL1 high-risk (HR) genotype was defined by the carriage of 2 risk alleles.ResultsIn West Africa (Burkina Faso and Senegal), the G1 and G2 allele frequencies were 13.3% and 10.7%, respectively. In Cameroon (Central Africa), G1 and G2 frequencies were 8.7% and 8.9%, respectively. APOL1 HR prevalence was 4.9% in West Africa and 3.4% in Cameroon. We found no direct association between APOL1 HR and estimated glomerular filtration rate (eGFR) change over time. Nevertheless, among the 2LADY cohort participants, those with both APOL1 HR and high baseline viral load had a faster eGFR progression (β = -3.9[-7.7 to -0.1] ml/min per 1.73 m2 per year, P < 0.05) than those with low-risk (LR) genotype and low viral load.ConclusionOverall, the APOL1 risk allele frequencies in PLHIV were higher in the West African countries than in Cameroon, but much lower than previously reported in some Nigeria ethnic groups, which strongly advocates for further investigation in the African continent. This study suggested that the virological status could modulate the APOL1 impact on kidney function, hence reinforcing the need for early therapeutic interventions.

| S-EPMC8897309 | biostudies-literature

APOL1 renal-risk variants induce mitochondrial dysfunction

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-08-23 | E-GEOD-85921 | biostudies-arrayexpress

APOL1 renal-risk variants induce mitochondrial fission

Project description:To assess gene expression by APOL1 genotypes in primary proximal tubule cells (PTCs), global gene expression (mRNA) levels were examined on Affymetrix HTA 2.0 arrays in primary PTCs cultured from non-diseased kidney in African Americans without CKD who underwent nephrectomy for localized renal cell carcinoma.

2018-09-15 | GSE119958 | GEO

APOL1 renal-risk variants induce mitochondrial dysfunction

Project description:This SuperSeries is composed of the SubSeries listed below.

2016-08-23 | GSE85921 | GEO

APOL1 renal-risk variants induce mitochondrial dysfunction (Illumina)

Project description:To elucidate pathways whereby apolipoprotein L1 gene (APOL1) G1 and G2 variants facilitate kidney disease in African Americans, human embryonic kidney cells (HEK293) were used to establish doxycycline-inducible (Tet-on) cell lines stably expressing reference APOL1 G0 and its G1 and G2 renal-risk variants. Illumina human HT-12-v4 arrays and Affymetrix HTA 2.0 arrays were employed to generate global gene expression data with doxycycline induction. Significantly altered pathways identified through bioinformatics involved mitochondrial function; results were validated using immunoblotting, immunofluorescence and functional assays. Global gene expression profiles were performed on HEK293 Tet-on G0, G1, G2 and empty vector cells with and without Dox induction using Illumina human HT-12 v4 arrays. Another independent gene expression array system, Affymetrix HTA 2.0, was used to verify the results of Illumina arrays. Pair-wise and pattern-based analyses were applied to detect the mostly impacted pathways due to overexpression and by APOL1 genotypes.

2016-08-23 | E-GEOD-85918 | biostudies-arrayexpress

Worldwide Frequencies of APOL1 Renal Risk Variants.

Project description: Not available

| S-EPMC6482949 | biostudies-literature

APOL1 risk variants predict histopathology and progression to ESRD in HIV-related kidney disease.

Project description:With earlier institution of antiretroviral therapy, kidney diseases other than HIV-associated nephropathy (HIVAN) predominate in HIV-infected persons. Outcomes for these diseases are typically worse among those infected with HIV, but the reasons for this are not clear. Here, we examined the role of APOL1 risk variants in predicting renal histopathology and progression to ESRD in 98 HIV-infected African Americans with non-HIVAN kidney disease on biopsy. We used survival analysis to determine time to ESRD associated with APOL1 genotype. Among the 29 patients with two APOL1 risk alleles, the majority (76%) had FSGS and 10% had hypertensive nephrosclerosis. In contrast, among the 54 patients with one APOL1 risk allele, 47% had immune-complex GN as the predominant lesion and only 23% had FSGS. Among the 25 patients with no APOL1 risk allele, 40% had immune-complex GN and 12% had FSGS. In 310 person-years of observation, 29 patients progressed to ESRD. In adjusted analyses, individuals with two APOL1 risk alleles had a nearly three-fold higher risk for ESRD compared with those with one or zero risk alleles (P=0.03). In summary, these data demonstrate an association between APOL1 variants and renal outcomes in non-HIVAN kidney disease, suggesting a possible use for APOL1 genotyping to help guide the care of HIV-infected patients.

| S-EPMC3269183 | biostudies-literature

APOL1 renal-risk variants induce mitochondrial dysfunction (Illumina)

2016-08-23 | GSE85918 | GEO

Association of APOL1 Genotype with Renal Histology among Black HIV-Positive Patients Undergoing Kidney Biopsy.

Project description:Background and objectivesPrior studies have shown that the APOL1 risk alleles are associated with a greater risk of HIV-associated nephropathy and FSGS among blacks who are HIV positive. We sought to determine whether the APOL1 high-risk genotype incrementally improved the prediction of these underlying lesions beyond conventional clinical factors.Design, setting, participants, & measurementsIn a cross-sectional study, we analyzed data from 203 blacks who are HIV positive, underwent kidney biopsies between 1996 and 2011, and were genotyped for the APOL1 G1 and G2 alleles. Predictive logistic regression models with conventional clinical factors were compared with those that also included APOL1 genotype using receiver-operating curves and bootstrapping analyses with crossvalidation.ResultsThe addition of APOL1 genotype to HIV-related risk factors for kidney disease in a predictive model improved the prediction of non-HIV-associated nephropathy FSGS, specifically, increasing the c statistic from 0.65 to 0.74 (P=0.04). Although two risk alleles were significantly associated with higher odds of HIV-associated nephropathy, APOL1 genotype did not add incrementally to the prediction of this specific histopathology.ConclusionsAPOL1 genotype may provide additional diagnostic information to traditional clinical variables in predicting underlying FSGS spectrum lesions in blacks who are HIV positive. In contrast, although APOL1 risk genotype predicts HIV-associated nephropathy, it lacked a high c statistic sufficient for discrimination to eliminate the role of kidney biopsy in the clinical care of blacks who are HIV positive with nephrotic proteinuria or unexplained kidney disease.

| S-EPMC4741048 | biostudies-literature

APOL1 renal-risk variants induce mitochondrial dysfunction (Affymetrix 2)

Project description:To assess differential gene expression by APOL1 renal-risk (2 risk alleles) vs. non-risk (G0G0) genotypes in primary proximal tubule cells (PTCs), global gene expression (mRNA) levels were examined on Affymetrix HTA 2.0 arrays in primary PTCs cultured from non-diseased kidney in African Americans without CKD who underwent nephrectomy for localized renal cell carcinoma. To detect differentially expressed gene profiles attributable to APOL1 renal-risk genotypes, African American primary proximal tubule cells with two APOL1 renal-risk alleles (N=5) and lacking renal-risk alleles (N=25) were included in comparisons of global gene expression.

2016-08-23 | E-GEOD-85920 | biostudies-arrayexpress

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