APOL1 renal risk variants are associated with obesity and body composition in African ancestry adults

Nadkarni, Girish N.; Fei, Kezhen; Galarneau, Geneviève; Gao, Yan; Wilson, James G.; Cooper, Richard S.; Madden, Ebony; Denny, Joshua C.; Richardson, Lynne D.; Pollak, Martin R.; Loos, Ruth J.F.; Horowitz, Carol R.

doi:10.1097/md.0000000000027785

Cited by 8 publications

(8 citation statements)

References 40 publications

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“…Third, regarding kidney disease risk, we showed an association with obesity and two APOL1 risk alleles but no demonstrable effect of obesity on the association of APOL1 with albuminuria. Our findings corroborate those of a similar-sized study of 11,930 African American participants, where each risk allele was associated with greater obesity odds (1.13-fold) (42), but this association has not been demonstrated in other large cohorts, such as the Coronary Artery Risk Development in Young Adults and the Atherosclerosis Risk in Communities studies (19,43). There was no effect of socioeconomic status on the association between APOL1 and albuminuria.…”

Section: Discussionsupporting

confidence: 89%

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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Section: Discussionsupporting

confidence: 89%

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

Brandenburg

Govender

Winkler

et al. 2022

CJASN

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“…Further, obesity prevalence rates differ significantly by race and ethnicity, with African Americans being 50% more likely to be obese than non-Hispanic whites [ 44 ], and African American children are at higher risk of being obese [ 45 , 46 , 47 ]. These results are in consistence with another study, affirming that AA is at a higher risk of obesity [ 48 ] and that race, along with the BMI status, is linked with DNA methylation of genes.…”

Section: Discussionmentioning

confidence: 99%

Racial Disparities in Methylation of NRF1, FTO, and LEPR Gene in Childhood Obesity

Patel

Selvaraju

Babu

et al. 2022

Genes

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Childhood obesity has affected the health of millions of children around the world despite vigorous efforts by health experts. The obesity epidemic in the United States has disproportionately afflicted certain racial and ethnic minority groups. African American children are more likely than other children to have obesity-related risk factors such as hyperlipidemia, diabetes, cardiovascular disease, and coronavirus disease (COVID-19). For the reduction in obesity-related health inequalities to be successful, it is essential to identify the variables affecting various groups. A notable advancement in epigenetic biology has been made over the past decade. Epigenetic changes like DNA methylation impact on many genes associated with obesity. Here, we evaluated the DNA methylation levels of the genes NRF1, FTO, and LEPR from the saliva of children using real-time quantitative PCR-based multiplex MethyLight technology. ALU was used as a reference gene, and the Percent of Methylated Reference (PMR) was calculated for each sample. European American children showed a significant increase in PMR of NRF1 and FTO in overweight/obese participants compared to normal weight, but not in African American children. After adjusting for maternal education and annual family income by regression analysis, the PMR of NRF1 and FTO was significantly associated with BMI z-score only in European American children. While for the gene LEPR, African American children had higher methylation in normal weight participants as compared to overweight/obese and no methylation difference in European American children. The PMR of LEPR was significantly negative associated with the obesity measures only in African American children. These findings contribute to a race-specific link between NRF1, FTO, and LEPR gene methylation and childhood obesity.

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“…Both the Jackson Health Study and the Women’s Health Initiative found that adult participants with two high-risk APOL1 alleles had an increased cardiovascular disease risk after correcting for traditional risk factors and CKD as compared with those without the high-risk alleles 26. High-risk variants were associated with BMI and obesity in an additive manner in a genotype-phenotype association study 27. Since APOL1 is an important component of HDL 3 particles that attenuate LDL oxidation, it may play a role in reverse cholesterol transport.…”

Section: Discussionmentioning

confidence: 99%

Obesity-related glomerulopathy in the presence of APOL1 risk alleles

Seng

Stokes

et al. 2022

BMJ Case Rep

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Nephropathic apolipoprotein L1 (APOL1) risk alleles (G1/G2) have been associated with focal segmental glomerulosclerosis, HIV-associated nephropathy, Systemic lupus erythematosus (SLE)-associated collapsing glomerulopathy and other glomerulonephritides. These alleles confer protection from Trypanosoma brucei infections which are enriched in sub-Saharan African populations. We present a young woman with obesity, hypertension, subnephrotic range proteinuria who was found to have obesity-related glomerulopathy on kidney biopsy while harbouring two high-risk APOL1 alleles (G1/G2). Given the potential effects on lipid metabolism and their association with obesity, the presence of APOL1 risk alleles may impact cardiovascular health in addition to renal disease in these patients.

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APOL1 renal risk variants are associated with obesity and body composition in African ancestry adults

Abstract: Supplemental Digital Content is available in the text

Cited by 8 publications

References 40 publications

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

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

Racial Disparities in Methylation of NRF1, FTO, and LEPR Gene in Childhood Obesity

Obesity-related glomerulopathy in the presence of APOL1 risk alleles

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