APOL1 Genetic Testing in Patients With Recent African Ancestry and Hypertension: A Pilot Study of Attitudes and Perceptions

Lentine, Krista L.; Muiru, Anthony N.; Çalışkan, Yaşar; Lindsay, Kathryn K.; Edwards, John C.; Memon, Aliza Anwar; Miyata, Kana N.; Mosman, Amy K.; Vo, Than-Mai; Freedman, Barry I.; Carriker, Amber; Hsu, Chi‐yuan; Philipneri, Marie

doi:10.1016/j.xkme.2022.100549

Cited by 5 publications

(3 citation statements)

References 12 publications

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“…While the potential associations described here require confirmation in other cohorts, they indicate a wide spectrum of conditions that are associated with APOL1 risk alleles, and particularly with the G1/G2 genotype. Previous studies have highlighted ethical considerations of such testing 42 , however strong support for testing has recently been reported among African Americans attending hypertension and nephrology clinics in the United States 43 , and disclosure of high-risk APOL1 genotypes to hypertension patients has led to reductions in blood pressure and lifestyle changes such as improved dietary and exercise habits 44 . An affordable, rapid, point-of-care test for APOL1 genotype would enable testing to be performed in both affluent and resource-poor settings and could have important implications at individual and population level by identifying those who would benefit from targeted early intervention and treatment.…”

Section: Discussionmentioning

confidence: 99%

Phenome-wide analysis ofAPOL1risk variants reveals associations between one combination of haplotypes and multiple disease phenotypes in addition to chronic kidney disease

Adamson

Noyes

Johnson

et al. 2023

Preprint

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Background Infectious diseases are a major driving force of natural selection. One human gene associated with strong evolutionary selection isAPOL1. TwoAPOL1variants, G1 and G2, emerged in sub-Saharan Africa in the last 10,000 years, possibly due to protection from the fatal African sleeping sickness, analogous toPlasmodium-driven selection of the sickle-cell trait. As homozygosity for the HbS allele causes sickle cell anaemia, homozygosity for theAPOL1G1 and G2 variants has also been associated with chronic kidney disease (CKD) and other kidney-related conditions. What is not known is the extend of non-kidney-related disorders and if there are clusters of diseases associated with individualAPOL1genotypes. Methods Using principal component analysis, we identified a cohort of 10,179 UK Biobank participants with recent African ancestry. We conducted a phenome-wide association test between all combinations ofAPOL1G1 and G2 genotypes and conditions identified with International Classification of Disease phenotypes using Firth's bias-reduced logistic regression and a false discovery rate to correct for multiple testing. We further examined associations with chronic kidney disease indicators: estimated glomerular filtration rate (eGFR) and urinary albumin:creatinine (uACR). Results The phenome-wide screen revealed 74 (mostly deleterious) potential associations with hospitalisation for a range of conditions. G1/G2 compound heterozygotes were specifically associated with hospitalisation in 64 (86.5%) of these conditions, with an over-representation of infectious diseases (including COVID-19) and endocrine, nutritional, and metabolic diseases. The analysis also revealed complexities in the relationship betweenAPOL1and CKD that are not evident when the risk variants are grouped together: high uACR was associated specifically with G1 homozygosity; low eGFR with G2 homozygosity and G1/G2 compound heterozygosity; progression to end stage kidney disease was associated with G1/G2 compound heterozygosity. Conclusions Among 9,594 participants, stratifying individualAPOL1risk variant genotypes had a differential effect on associations with both kidney and non-kidney phenotypes. The compound heterozygous G1/G2 genotype was distinguished as uniquely deleterious in its association with a range of ICD-10 phenotypes. The epistatic nature of the G1/G2 interaction means that such associations may go undetected in a standard genome-wide association study. These observations have the potential to significantly impact the way that health risks are understood, particularly in populations whereAPOL1G1 and G2 are common such as in sub-Saharan Africa and its diaspora.

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Section: Discussionmentioning

confidence: 99%

Phenome-wide analysis ofAPOL1risk variants reveals associations between one combination of haplotypes and multiple disease phenotypes in addition to chronic kidney disease

Adamson

Noyes

Johnson

et al. 2023

Preprint

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“…This position is consistent with earlier work on Black attitudes toward ApoL1 testing. 20,21,28,46 Our project succeeded in achieving a consensus on one or more acceptable option for each clinical policy question. In most cases, our panel offers several acceptable options.…”

Section: Discussionmentioning

confidence: 99%

Evaluating ApoL1 Genetic Testing Policy Options for Transplant Centers

McIntosh,

Walsh,

Baldwin

et al. 2024

CJASN

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Background: ApoL1 variants G1 and G2 are associated with a higher risk of kidney disease. ApoL1 risk variants are predominantly seen in individuals with sub-Saharan African ancestry. In most transplant centers, potential organ donors are being selectively genetically tested for ApoL1 risk variants. Transplant programs have highly variable ApoL1 testing practices and need guidance on essential ApoL1 clinical policy questions. Methods: We conducted a Delphi consensus panel focused on ApoL1 clinical policy questions, including who gets tested, who decides whether testing occurs, how test results are shared, who receives test results, and how test results are used. A total of 27 panelists across 7 stakeholder groups participated: living kidney donors (n=4), deceased donor family members (n=3), recipients of a deceased donor kidney (n=4), recipients of a living donor kidney (n=4), nephrologists (n=4), transplant surgeons (n=4), and genetic counselors (n=4). Nineteen panelists (70%) identified as Black or African American. The Delphi panel process involved two rounds of educational webinars and three rounds of surveys administered to panelists, who were asked to indicate whether they support, could live with, or oppose each policy option. Results: The panel reached consensus on one or more acceptable policy options for each clinical policy question; panelists supported 18 policy options and opposed 15. Key elements of consensus include: Ask potential donors about African ancestry rather than race; make testing decisions only after discussion with donors; encourage disclosure of test results to blood relatives and organ recipients but do not require it; use test results to inform decision-making, but never for unilateral decisions by transplant programs. Conclusions: The panel generally supported policy options involving discussion and shared decision-making among patients, donors, and family stakeholders. There was general opposition to unilateral decision-making and prohibiting donation altogether.

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“…Strong support for APOL1 testing has been reported in the African American community 9 ; yet, the use of genetic testing in the evaluation of African American potential kidney donors has been a source of controversy in the transplant community. 10 , 11 On the one hand, genetic information may facilitate the identification of African American kidney donors at a greater risk of CKD and provide reassurance to those who are not.…”

mentioning

confidence: 99%

Ethical Challenge of Apolipoprotein L1 Testing in Potential Kidney Donors: A Case-Based Editorial

Danovitch¹,

Abdelnour²

2023

Kidney Medicine

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APOL1 Genetic Testing in Patients With Recent African Ancestry and Hypertension: A Pilot Study of Attitudes and Perceptions

Cited by 5 publications

References 12 publications

Phenome-wide analysis ofAPOL1risk variants reveals associations between one combination of haplotypes and multiple disease phenotypes in addition to chronic kidney disease

Phenome-wide analysis ofAPOL1risk variants reveals associations between one combination of haplotypes and multiple disease phenotypes in addition to chronic kidney disease

Evaluating ApoL1 Genetic Testing Policy Options for Transplant Centers

Ethical Challenge of Apolipoprotein L1 Testing in Potential Kidney Donors: A Case-Based Editorial

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