Dataset Information

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

ABSTRACT:

Background and objectives

Recessive 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, & measurements

This 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.

Results

High 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.

Conclusions

APOL1 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.

Podcast

This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_05_16_CJN14321121.mp3.

SUBMITTER: Brandenburg JT

PROVIDER: S-EPMC9269651 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Brandenburg Jean-Tristan JT Govender Melanie A MA Winkler Cheryl A CA Boua Palwende Romuald PR Agongo Godfred G Fabian June J Ramsay Michèle M

Clinical journal of the American Society of Nephrology : CJASN 20220516 6

<h4>Background and objectives</h4>Recessive inheritance of African-specific <i>APOL1</i> 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 <i>APOL1</i> risk variants on kidney disease in continental Africans is understudied. Objectives of this study were to determine <i>APOL1</i> risk allele prevalence and associations between <i>APOL1</i> genotypes and kidney dis ...[more]

PMID: 35577564

Similar Datasets

Project description:Hepatitis B virus (HBV) places a substantial health burden on Africa. Here, we investigated genetic diversity of HBV variants circulating in 4 countries of sub-Saharan Africa using archived samples. In total, 1492 plasma samples were tested from HIV-infected individuals and pregnant women, among which 143 (9.6%) were PCR-positive for HBV DNA (Côte d'Ivoire, 70/608 [11.5%]; Ghana, 13/444 [2.9%]; Cameroon, 33/303 [10.9%]; and Uganda, 27/137 [19.7%]).Phylogenetic analysis of the S-gene sequences identified HBV genotypes E (HBV/E, n=96) and A (HBV/A, n=47) distributed as follows: 87% of HBV/E and 13% of HBV/A in Côte d'Ivoire; 100% of HBV/E in Ghana; 67% of HBV/E and 33% of HBV/A in Cameroon; and 100% of HBV/A in Uganda. The average and maximal nucleotide distances among HBV/E sequences were 1.9% and 6.4%, respectively, suggesting a greater genetic diversity for this genotype than previously reported (p<0.001). HBV/A strains were classified into subgenotypes HBV/A1, HBV/A2 and HBV/A3. In Uganda, 93% of HBV/A strains belonged to HBV/A1 whereas HBV/A3 was the only subgenotype of HBV/A found in Cameroon. In Côte d'Ivoire, HBV/A strains were classified as HBV/A1 (11.1%), HBV/A2 (33.3%) and HBV/A3 (55.6%). Phylogeographic analysis of the sequences available from Africa supported earlier suggestions on the origin of HBV/A1, HBV/A2 and HBV/A3 in East, South and West/Central Africa, respectively. Using predicted amino acid sequences, hepatitis B surface antigen (HBsAg) was classified into serotype ayw4 in 93% of HBV/E strains and adw2 in 68% of HBV/A strains. Also, 7.7% of the sequences carried substitutions in HBsAg associated with immune escape.The observations of pan-African and global dissemination of HBV/A1 and HBV/A2, and the circulation of HBV/E and HBV/A3 almost exclusively in West and Central Africa suggest a more recent increase in prevalence in Africa of HBV/E and HBV/A3 compared to HBV/A1 and HBV/A2. The broad genetic heterogeneity of HBsAg detected here may impact the efficacy of prevention and control efforts in sub-Saharan Africa.

Project description:ObjectiveTwo apolipoprotein L1 (APOL1) risk variants (RV) are enriched in sub-Saharan African populations due to conferred resistance to Trypanosoma brucei. These variants associate with adverse renal outcomes by multiple causes including SLE. Despite emerging reports that SLE is common in Ghana, where APOL1 variant allelic frequencies are high, the regional contribution to SLE outcomes has not been described. Accordingly, this prospective longitudinal cohort study tested the associations between APOL1 high-risk genotypes and kidney outcomes, organ damage accrual and death in 100 Ghanaian patients with SLE.MethodsThis was a prospective cohort study of 100 SLE outpatients who sought care at Korle bu Teaching Hospital in Accra, Ghana. Adult patients who met 4 American College of Rheumatology criteria for SLE were genotyped for APOL1 and followed longitudinally for SLE activity as measured by the Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) hybrid and organ injury as measured by the Systemic Lupus International Collaborating Clinics Damage Index (SDI) at baseline and every 6 months for 1 year. Outcomes of interest were kidney function, SDI and case fatality.ResultsAssuming a recessive inheritance, the APOL1 high-risk genotype (2RV) associated with end-stage renal disease (ESRD) at an OR of 14 (p=0.008). These patients accrued more SDI points particularly in renal and neurological domains. The SDI was 81.3% higher in 2RV patients compared with 0RV or 1RV patients despite no difference in SLE activity (p=0.01). After a 12-month period of observation, 3/12 (25%) of the 2RV patients died compared with 2/88 (2.3%) of the 0RV or 1RV carriers (OR=13.6, p=0.01). Deaths were due to end-stage kidney disease and heart failure.ConclusionAPOL1 RVs were heritable risk factors for morbidity and mortality in this Ghanaian SLE cohort. Despite no appreciable differences in SLE activity, APOL1 high-risk patients exhibited progressive renal disease, organ damage accrual and a 13-fold higher case fatality.

Project description:Introduction: Investigating variation in genes involved in the absorption, distribution, metabolism, and excretion (ADME) of drugs are key to characterizing pharmacogenomic (PGx) relationships. ADME gene variation is relatively well characterized in European and Asian populations, but data from African populations are under-studied-which has implications for drug safety and effective use in Africa. Results: We identified significant ADME gene variation in African populations using data from 458 high-coverage whole genome sequences, 412 of which are novel, and from previously available African sequences from the 1,000 Genomes Project. ADME variation was not uniform across African populations, particularly within high impact coding variation. Copy number variation was detected in 116 ADME genes, with equal ratios of duplications/deletions. We identified 930 potential high impact coding variants, of which most are discrete to a single African population cluster. Large frequency differences (i.e., >10%) were seen in common high impact variants between clusters. Several novel variants are predicted to have a significant impact on protein structure, but additional functional work is needed to confirm the outcome of these for PGx use. Most variants of known clinical outcome are rare in Africa compared to European populations, potentially reflecting a clinical PGx research bias to European populations. Discussion: The genetic diversity of ADME genes across sub-Saharan African populations is large. The Southern African population cluster is most distinct from that of far West Africa. PGx strategies based on European variants will be of limited use in African populations. Although established variants are important, PGx must take into account the full range of African variation. This work urges further characterization of variants in African populations including in vitro and in silico studies, and to consider the unique African ADME landscape when developing precision medicine guidelines and tools for African populations.

Dataset Information

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

Background and objectives

Design, setting, participants, & measurements

Results

Conclusions

Podcast

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets