APOL1 at 10 years: progress and next steps

Freedman, Barry I.; Kopp, Jeffrey B.; Sampson, Matthew G.; Suszták, Katalin

doi:10.1016/j.kint.2021.03.013

Cited by 15 publications

(13 citation statements)

References 62 publications

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“…Our study indicates that the phenotypic heterogeneity observed with RV APOL1 is related to the cell type of expression. Most prior studies have focused on podocyte RV APOL1 expression, which plays a key role in a rare form of glomarular disease ll Article (Freedman et al, 2021). Circulating APOL1 (which mostly originates from the liver) is important for trypanosome defense.…”

Section: Discussionmentioning

confidence: 99%

APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis

Raman

et al. 2021

Immunity

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Section: Discussionmentioning

confidence: 99%

APOL1 risk variants in individuals of African genetic ancestry drive endothelial cell defects that exacerbate sepsis

Raman

et al. 2021

Immunity

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“…Subsequent studies showed that APOL1 risk alleles were not associated with diabetic or IgA nephropathy but were associated with collapsing glomerulopathies due to systemic lupus erythematosus, exogenous interferon (IFN) administration, untreated HIV infection, and, more recently, severe acute respiratory syndrome coronavirus 2 (6,(11)(12)(13)(14)(15). To date, the spectrum of APOL1-associated disease includes sickle cell nephropathy, preeclampsia, FSGS, and hypertensionattributed kidney disease (16). In the African American population, APOL1 allele frequencies are approximately 23% for G1 and 13% for G2 (6).…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein L1 High-Risk Genotypes and Albuminuria in Sub-Saharan African Populations

Brandenburg

Govender

Winkler

et al. 2022

CJASN

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Background and objectivesRecessive inheritance of African-specific APOL1 kidney risk variants is associated with higher risk of nondiabetic kidney disease, progression to kidney failure, and early-onset albuminuria that precedes eGFR decline. The effect of APOL1 risk variants on kidney disease in continental Africans is understudied. Objectives of this study were to determine APOL1 risk allele prevalence and associations between APOL1 genotypes and kidney disease in West, East, and South Africa.Design, setting, participants, & measurementsThis cross-sectional population-based study in four African countries included 10,769 participants largely aged 40–60 years with sociodemographic and health information, anthropometry data, and blood and urine tests for biomarkers of kidney disease. APOL1 risk alleles were imputed from the H3Africa genotyping array, APOL1 risk allele and genotype frequencies were determined, and genetic associations were assessed for kidney disease. Kidney disease was defined as the presence of eGFR <60 ml/min per 1.73 m2, albuminuria, or a composite end point including eGFR <60 ml/min per 1.73 m2 and/or albuminuria.ResultsHigh G1 allele frequencies occurred in South and West Africa (approximately 7%–13%). G2 allele frequencies were highest in South Africa (15%–24%), followed by West Africa (9%–12%). Associations between APOL1 risk variants and albuminuria were significant for recessive (odds ratio, 1.63; 95% confidence interval, 1.25 to 2.12) and additive (odds ratio, 1.39; 95% confidence interval, 1.09 to 1.76) models. Associations were stronger for APOL1 G1/G1 genotypes versus G0/G0 (odds ratio, 3.87; 95% confidence interval, 2.16 to 6.93) compared with either G2/G2 (odds ratio, 1.65; 95% confidence interval, 1.09 to 2.51) or G1/G2 (odds ratio, 1.24; 95% confidence interval, 0.83 to 1.87). No association between APOL1 risk variants and eGFR <60 ml/min per 1.73 m2 was observed.ConclusionsAPOL1 G1 and G2 alleles and high-risk genotype frequencies differed between and within West and South Africa and were almost absent from East Africa. APOL1 risk variants were associated with albuminuria but not eGFR <60 ml/min per 1.73 m2. There may be differential effects of homozygous G1 and G2 genotypes on albuminuria that require further investigation.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_05_16_CJN14321121.mp3

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“…This excess chronic kidney disease (CKD) risk can mostly be explained by G1 and G2 coding variants in apolipoprotein L1 (APOL1; refs. [3][4][5]. APOL1 is a recently evolved member of the APOL gene family only found in humans and certain higher-order primates.…”

Section: Introductionmentioning

confidence: 99%