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Genetic risk of APOL1 and kidney disease in children and young adults of African ancestry.

ABSTRACT: PURPOSE OF REVIEW:Understanding the genetic risk of APOL1 in children and young adults is important given the lifetime risk of hypertension and kidney disease among children of African descent. We review recent epidemiologic and biologic findings on the effects of APOL1 and kidney disease. RECENT FINDINGS:APOL1 in children and young adults is associated with hypertension, albuminuria and more rapid decline in kidney function and progression to end-stage kidney disease, especially among those with glomerular causes of kidney disease, and those affected by sickle cell disease or HIV. There are conflicting data on the APOL1 association with cardiovascular disease in children and young adults. APOL1 functions as part of the innate immune system. Podocyte expression of APOL1 likely contributes to the development of kidney disease. In cell culture and model organisms, APOL1 expression disrupts autophagic and ion flux, leads to defects in mitochondrial respiration and induces cell death. SUMMARY:APOL1 explains almost 70% of the excess risk of kidney disease in those of African descent, and is common in children with glomerular disease. An evolving understanding of the pathogenesis of APOL1-mediated kidney damage may aid in personalized medicine approaches to APOL1 attributable kidney disease.

SUBMITTER: Reidy KJ

PROVIDER: S-EPMC6002812 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Genetic risk of APOL1 and kidney disease in children and young adults of African ancestry.

Reidy Kimberly J KJ Hjorten Rebecca R Parekh Rulan S RS

Current opinion in pediatrics 20180401 2

<h4>Purpose of review</h4>Understanding the genetic risk of APOL1 in children and young adults is important given the lifetime risk of hypertension and kidney disease among children of African descent. We review recent epidemiologic and biologic findings on the effects of APOL1 and kidney disease.<h4>Recent findings</h4>APOL1 in children and young adults is associated with hypertension, albuminuria and more rapid decline in kidney function and progression to end-stage kidney disease, especially ...[more]

PMID: 29406442

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Project description:Abstract While increased obesity prevalence among persons of African ancestry (AAs) compared to persons of European ancestry (EAs) is linked to social, environmental and behavioral factors, there are no gene variants that are common and significantly associated with obesity in AA populations. We sought to explore the association between ancestry specific renal risk variants in the apolipoprotein L1 (APOL1) gene with obesity related traits in AAs. We conducted a genotype–phenotype association study from 3 electronic medical record linked cohorts (BioMe Biobank, BioVU, nuGENE); randomized controlled trials (genetic testing to understand and address renal disease disparities) and prospective cohort study (Jackson Heart Study). We analyzed association of APOL1 renal risk variants with cross-sectional measures of obesity (average body mass index (BMI), and proportion of overweight and obesity) and with measures of body composition (in Jackson Heart Study). We had data on 11,930 self-reported AA adults. Across cohorts, mean age was from 42 to 49 years and percentage female from 58% to 75.3%. Individuals who have 2 APOL1 risk alleles (14% of AAs) have 30% higher obesity odds compared to others (recessive model adjusted odds ratio 1.30; 95% confidence interval 1.16–1.41; P = 2.75 × 10−6). An additive model better fit the association, in which each allele (47% of AAs) increases obesity odds by 1.13-fold (adjusted odds ratio 1.13; 95% confidence interval 1.07–1.19; P = 3.07 × 10−6) and increases BMI by 0.36 kg/m2 (∼1 kg, for 1.7 m height; P = 2 × 10−4). APOL1 alleles are not associated with refined body composition traits overall but are significantly associated with fat free mass index in women [0.30 kg/m2 increment per allele; P = .03]. Thus, renal risk variants in the APOL1 gene, found in nearly half of AAs, are associated with BMI and obesity in an additive manner. These variants could, either on their own or interacting with environmental factors, explain a proportion of ethnic disparities in obesity.

Dataset Information

Genetic risk of APOL1 and kidney disease in children and young adults of African ancestry.

Publications

Genetic risk of APOL1 and kidney disease in children and young adults of African ancestry.

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