APOL1, Black Race, and Kidney Disease: Turning Attention to Structural Racism

The incidence of kidney failure is nearly 3 times higher in Black relative to White Americans.1Saran R. Robinson B. Abbott K.C. et al.US Renal Data System 2018 Annual Report: epidemiology disease the United States.Am J Kidney Dis. 2019; 73 (3)(suppl 1):A7-A8Abstract Full Text PDF PubMed Scopus (448) Google Scholar A significant body biomedical literature links this racial inequity polymorphic variation gene encoding apolipoprotein L1 (APOL1). In fact, a search “APOL1” and “kidney disease,” 86% results feature abstracts mentioning African ancestry or American, Black, non-White race. Multiple recent articles state that APOL1 genetic variants are found “exclusively” people, chromosomes, “African” origin.2Kopp J.B. Winkler C.A. Genetics, genomics, precision medicine end-stage disease.Semin Nephrol. 2018; 38: 317-324Abstract (7) Scholar, 3Cheatham A.M. Davis S.E. Khatua A.K. Popik W. Blocking 5? splice site exon 4 by morpholino oligomer triggers protein isoform switch.Sci Rep. 8: 8739Crossref (8) 4Hughson M.D. Hoy W.E. Mott S.A. Bertram J.F. Kopp risk independently associated with early cardiovascular death.Kidney Int 3: 89-98Abstract (10) Further, an ongoing clinical trial—the Long-term Transplantation Outcomes Network (APOLLO) study—seeks examine relationship between genotype disparities allograft survival among living donors.5Freedman B.I. Moxey-Mims M.M. Alexander A.A. al.APOL1 (APOLLO): design rationale.Kidney 2020; 5: 278-288Abstract (28) Such tight coupling race lends impression genetically determined homogeneously distributed across persons labeled as “Black,” misguided hypothesis can skew investment toward interventions limited effect. editorial, we summarize current on APOL1, discuss scientific flaws linking particular race, emphasize role structural racism determinant disease. Genetic chromosome 22q has been increased susceptibility focal segmental glomerulosclerosis, HIV-associated nephropathy, hypertension-attributed failure. particular, strong signals have identified association 2 nonsynonymous coding (for amino acids 342 384) termed G1, 6-base-pair deletion removes (388-389), G2.6Genovese G. Friedman D.J. Ross al.Association trypanolytic ApoL1 Americans.Science. 2010; 329: 841-845Crossref (1340) Patterns linkage disequilibrium region G1 G2 provide evidence for positive selection. because evade activity serum resistance–associated T. b. rhodiense—one vectors sleeping sickness—it hypothesized heterozygosity these alleles confers selective advantage against disease.7Thomson Genovese Canon C. al.Evolution primate factor APOL1.PNAS. 2014; 111: E2130-E2139Crossref (152) Furthermore, presence Yoruban populations from Nigeria some Americans, their scarcity European Asian populations, evince likelihood selection event West Africa.6Genovese Scholar,8Simino J. Rao D.C. Freedman Novel findings future directions genetics hypertension.Curr Opin Nephrol Hypertens. 2012; 21: 500-507Crossref (34) Together, data led investigators focus polymorphisms key, rather than contributory, explanatory variable For instance, Winkler9Kopp testing practice: finally starting arrive.CJASN. 15: 126-128Crossref (11) name “variants major driver[s] Blacks” accordingly recommendations genotypes. This approach, however, based upon misapplication population exacerbated conflation Race social political construct perpetuated those power should not be used substitute thoughtful, hypothesis-driven analyses.10Tsai Cerdeña J.P. Khazanchi al.There no ‘African American Physiology’: fallacy essentialism.J Intern Med. 288: 368-370Crossref (12) Human phenotypic variants, including superficial physical differences like skin color hair texture, clinally geographic space do map neatly races continents.11American Association Physical AnthropologistsAAPA statement & racism. March 27, 2019.https://physanth.org/about/position-statements/aapa-statement-race-and-racism-2019Google Scholar,12The Society GeneticsASHG denounces attempts link supremacy.Am Hum Genet. 103: 636Abstract (35) Researchers may lean terms “ancestry,” which imply evolutionary history carry biological significance at individual level analysis13Yudell M. Roberts D. DeSalle Tishkoff S. Taking out human genetics.Science. 2016; 351: 564-565Crossref (294) Scholar,14Bolnick Individual inference reification phenomenon.in: Lee Koenig Richardson S.S. Revisiting Genomic Age. Rutgers University Press, 2008: 70-85Google Scholar; when paired wide geographical modifier (ie, “African”), such phrases lose meaning become little more conclusions cannot made about entire continents races; accordingly, discussing APOL1-associated concern of—and exclusive to—people “African descent” reflects racist practice research,15Cerdeña Plaisime M.V. Tsai From race-based race-conscious medicine: how anti-racist uprisings call us act.Lancet. 396: 1125-1128Abstract (93) even if often done unconsciously. section, identify specific inherent logic associating outline potential harms patients. Sweeping associations certain overlooking impact nephropathy other populations. Although most seen people descent, groups—including Pakistani, Latin patients—also polymorphisms.16Kopp Nelson G.W. Sampath K. glomerulosclerosis nephropathy.J Am Soc 2011; 22: 2129-2137Crossref (557) 17Limou alleles: associations.Adv Chronic 426-433Abstract (113) 18Nadkarni G.N. Gignoux C.R. Sorokin E.P. al.Worldwide frequencies renal variants.N Engl 379: 2571-2572Crossref (41) Even though likely owing admixture, suggest limiting inquiries “Black” patients inappropriately excludes ethnic backgrounds. APOLLO study, only recruits donors, restricting insights into outcomes artificially smaller population. reluctant generalize White, Asian, Latinx who would otherwise benefit. Moreover, frequency varies widely continent. Igbo 30.2% but 0% Lemande Cameroon.17Limou Yet, both groups racialized States. Additionally, similar groups, allelic evident. research comparing genotypes Yoruba Luhya Kenya, high similarity, sites were differentiated G1. large explained drift instead points occurring within narrowly circumscribed Africa.7Thomson Therefore, generalized all residents continent, nor individuals descent. Because many enslaved Africans captured coast during trans-Atlantic slave trade, Americans descended slaves expected exhibit G2. Indeed, suggests over 20% 1 13% 2.19Dummer P.D. Limou Rosenberg A.Z. variants: evolving landscape.Semin 2015; 35: 222-236Abstract (98) However, patterns migration reveal influx Northern Eastern Africa, regions where far less prevalent.20Capps McCabe Fix Diverse Streams: Migration Policy Institute, 2012: 1-23https://www.fcd-us.org/assets/2016/04/African-Migration-to-the-United-States.pdfGoogle Accordingly, given continued inflow migrants diverse Africa—and admixture descendants distinct populations—wide heterogeneity expected, depending sampling. summary, sweeping attributions overlook increasing diversity community others. Incautious promote misinformed experience predisposition disease.21Gordon E.J. Amórtegui Blancas I. Wicklund Friedewald Sharp R.R. group study donors’ treatment preferences, sociocultural factors, health beliefs testing.Prog Transpl. 29: 239-247Crossref (5) reflected Donor Risk Index, tool includes its calculation longevity donated kidneys. Substitution equation improve Index 85% 90% reducing discard high-demand kidneys.22Julian B.A. Gaston R.S. Brown W.M. al.Effect replacing donor index.Am Transplant. 2017; 17: 1540-1548Crossref (42) Thus, generalizations scientifically inappropriate contribute care waste. Finally, straightforward implies. possessing “risk” yields odds ratio 10.5 7.3 failure, respectively,6Genovese overall lifetime just 4% 12%. explains 37%, 18%, 7% variance respectively,19Dummer while reports find diabetic leading cause disease.17Limou account roughly 30% excess nondiabetic Americans,23Kaufman J.S. Rushani Cooper Nature versus nurture explanations racial/ethnic disparities.in: Suzuki Von Vacano D.A. Reconsidering Race: Social Science Perspectives Racial Categories Age Genomics. Oxford 2018: 120Google highlighting importance environmental factors underpinning clearly demarcated variation; States, histories inequitable distribution resources along lines systematically created unequal environments life opportunities communities, differentially health. Structural refers “the totality ways societies foster discrimination through mutually reinforcing systems.”24Bailey Z.D. Krieger N. Agénor Graves Linos Bassett M.T. inequities USA: interventions.Lancet. 389: 1453-1463Abstract (1534) Disparities derive conditions wealth, employment, residence, toxic exposures, nutrition, education, access, psychosocial stress.25Nicholas S.B. Kalantar-Zadeh Norris outcomes.Semin 2013; 33: 409-415Abstract (87) 26Laster Shen J.I. Americans: perspective.Am 72: S3-S7Abstract 27Young Interaction Race, Poverty, CKD.Am 55: 977-980Abstract (14) 28Norris Mehrotra Nissenson A.R. mortality disease.Am 2008; 52: 205-208Abstract (19) 29Crews Purnell T.S. COVID-19, racism, disease: galvanizing response.JASN. 31: 1-3Crossref Mediators failure—such diabetes, hypertension, HIV—can traced racialization US food system,30Ayazi H. Elsheikh E. Farm Bill: Corporate Power Racialization Food System. UC Berkeley Othering Belonging Institute. October 28, 2015.https://escholarship.org/uc/item/55v6q06xGoogle mass incarceration,31Wang E.A. Pletcher Lin F. al.Incarceration, incident access care: Coronary Artery Development Young Adults (CARDIA) Study.Arch 2009; 169: 687-693Crossref (88) poverty.32Arnold Rebchook G.M. Kegeles S.M. “Triply cursed”: homophobia HIV-related stigma barriers regular HIV testing, adherence disclosure young gay men.Cult Health Sex. 16: 710-722Crossref (226) determinants thereby deserve least dedicated afforded inquiry, yet funding streams consistently favor investigation underpinnings issues racialization.33Hardeman Karbeah Examining services research: disciplinary self-critique.Health Serv Res. 777-780Crossref (55) Scholar,34Krieger Stormy weather: expression, science disparities.Am Public Health. 2005; 95: 2155-2160Crossref (155) simple Boolean disease” “racism” National Institutes Research Portfolio Online Reporting Tools Database 2019 2020 5 results, whereas pairing “genetic” 754 results.33Hardeman Racism itself induce multiple physiologic changes involved pathogenesis stress interpersonal initiate long-term activation hypothalamic-pituitary-adrenal axis, constitutively increase vascular tension. also lead downregulate inflammatory response production reactive oxygen species, interstitial fibrosis.25Nicholas epigenetic modifications—such resulting fetal programming increases prenatal cortisol exposure—may Americans.35Kuzawa C.W. Sweet Epigenetics embodiment race: developmental origins health.Am Biol. 2-15Crossref (416) although poor proxy genetics, adverse experienced marginalized consistent powerful contributors risk. Overemphasis genetics—rather racism—may result insufficient examination Future racist—and antiracist—policies affect Studies assess effects policies Medicaid expansion,36Sommers B.D. Blendon R.J. Orav Epstein Changes utilization low-income adults after expansion expanded private insurance.JAMA 176: 1501-1509Crossref (317) Scholar,37Kurella-Tamura Goldstein Hall Y.N. Mitani Winkelmayer W.C. State coverage, ESRD incidence, care.JASN. 25: 1321-1329Crossref decriminalization,38Grucza R.A. Vuolo Krauss M.J. al.Cannabis decriminalization: policy change five U.S. states.Int Drug Policy. 59: 67-75Crossref (24) or, future, reparations39Vigdor North Carolina City Approves Reparations Residents. New York Times. July 16, section A:15.https://www.nytimes.com/2020/07/16/us/reparations-asheville-nc.htmlGoogle carefully analyzed: merely examines “risk factor”—or provides basis outcomes—should scrupulously critiqued.40Boyd R.W. Lindo E.G. Weeks L.D. McLemore M.R. On Racism: Standard Publishing Inequities. Affairs: Affairs Blog. 2, 2020.https://www.healthaffairs.org/do/10.1377/hblog20200630.939347/full/Google Understanding inform public action, dismantling oppressive structures disparities. Carrying significantly individual’s developing disease; high-risk genotype, remains relatively low much levels shameful chattel slavery, allele “Black.” It therefore conclude mutations limit individuals: determinations constrain decision making misdirect detriment Decisions regarding engage key stakeholders, patients, nephrologists, primary providers, researchers, bioethicists, considering patient counseling need develop targeted treatments.41Young Blacksher Cavanaugh K.L. al.Apolipoprotein involving discussions.Am 50: 303-311Crossref since fully explain disease, mediates impairments function deserves closer attention.