APOL 1 Risk Genotype is associated with Albuminuria in Sub-Saharan African without Hypertension: A Case Study of Trypanosoma Brucei Gambiense Endemic Area
DOI:
https://doi.org/10.47941/ijhmnp.1723Keywords:
APOL1 - Hypertension Trypanosomiasis Endemic Area – AlbuminuriaAbstract
Purpose. An association between APOL1 risk genotypes (HRG) and hypertension has been reported in African Americans with chronic kidney diseases (CKD). However, such data from African populations living in a Human African Trypanosomiasis (HAT) endemic area remain limited.This study assessed the association between APOL1 high-risk genotypes (HRG) and hypertension among sub-Saharan African in T.b. gambiense endemic area.
Methodology. This cross-sectional study enrolled 94 HAT-infected and 144 non–infected participants in Masimanimba, the Democratic Republic of the Congo, from April 2019 to April 2021. We evaluated the association between APOL1 HRG and hypertension in HAT-infected and non–infected participants. APOL1 HRG was defined as the presence of two risk variants (G1/G1, G2/G2, or G1/G2), and a low-risk genotype (LRG) with the presence of 0 or 1 single variant. The elevated albuminuria was defined as urinary albumin/creatinine ratio ≥ 30 mg/g. Student’s and Pearson's Chi2 tests or Fisher’s exact test were used to compare means and proportions. The Wilcoxon/Mann–Whitney test was used to compare medians. A multivariate logistic regression model was used to identify independent determinants of hypertension. Odds ratios were provided with their 95% confidence intervals (Cis). Statistical significance was set at p < 0.05, based on 2-tailed test.
Findings. APOL1 sequence analysis revealed that 3 of 21 (14.3%) hypertensive participants carried HRG (G1G1) and 7 of 103 (6.8%) non-hypertensive carried HRG (G1G1, G2G2, and G1G2) (p=0.371). The frequency of APOL1 HRG among hypertensive participants was 14.3% in both HAT- infected and uninfected individuals. Ten of 21 (47.6%) hypertensive individuals with elevated albuminuria had a higher incidence of CKD (100% vs. 0%; p < 0.001) and HRG (30% vs. 0%; p = 0.09) than 11 (52.3%) without albuminuria who carried LRG. Of 103 non-hypertensive subjects, 43 (41.7%) with elevated albuminuria had a higher frequency of HRG (16.3% vs. 0%; p = 0.002) and CKD (100% vs. 1.7%; p<0.001) compared with 60 of 103 (58.3%) without albuminuria who carried LRG.
Unique contributor to theory, policy and practice: APOL1 HRG was associated with albuminuria and CKD, regardless of the hypertension status in T.b. gambiense HAT endemic area. However, further prospective cohort studies are required to confirm these results. The High-risk subjects will benefit from early preventive measures in low-income countries.
Downloads
References
World Health Organization. Hypertension. Mars 2023, World Health Organization. https://www.who.int/news-room/fact-sheets/detail/hypertension.
Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the United States, 1988–2000. JAMA. 2003; 290:199–206. [PubMed: 12851274])
Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M et al. Heart disease and stroke statistics—2016 update: a report from the American Heart Association. Circulation. 2016; 133:e38–360. [PubMed: 26673558])
Nadkarni GN, Galarneau G, Ellis SB, Nadukuru R, Zhang J, Scott SA et al. Apolipoprotein L1 variants and blood pressure traits in African Americans. J Am Coll Cardiol. 2017; 69(12):1564–74. doi: 10.1016/j.jacc.2017.01.040
Genovese G , Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, et al. Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010; 329(5993):841–45. [PubMed: 20647424]
Lipkowitz MS, Freedman BI, Langefeld CD, Comeau ME, Bowden DW, Linda Kao W.H. et al. Apolipoprotein L1 gene variants associate with hypertension-attributed nephropathy and the rate of kidney function decline in African Americans. Kidney Int. 2013; 83 (1):114–20. [PubMed: 22832513]
Friedman DJ, Pollak MR: Genetics of kidney failure and the evolving story of APOL1. J Clin Invest. 2011; 121 (9) :3367–74.
Cooper A., Ilboudo H, Alibu., Ravel S, Enyaru J, Weir W et al. APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis. 2017;6:e25461. doi: 10.7554/eLife.2546.
Bryan Williams, Giuseppe Mancia, Wilko Spiering, Enrico Agabiti Rosei, Michel Azizi, Michel Burnier, et al. ESC Scientific Document Group , 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH), European Heart Journal, Volume 39, Issue 33, 01 September 2018, Pages 3021–3104, https://doi.org/10.1093/eurheartj/ehy339
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr et al. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee. Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003 Dec; 42(6):1206-52. doi: 10.1161/01.HYP.0000107251.49515.c2. Epub 2003 Dec 1. PMID: 14656957.
Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J. 2018; 39 (33) :3021–3104.
KG Alberti, Robert H Eckel, Scott M Grundy, Paul Z Zimmet, James I Cleeman, Karen A Donato et al. Harmonizing the Metabolic Syndrome. A Joint Interim Statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120(16):1640-45.
Browning L, Hsieh S, Ashwell M. A Systematic review of waist-to-height ratio as a screening tool for the prediction of cardiovascular disease and diabetes could be a suitable global boundary value. Nutr Res Rev 2010; 23(2):247–69
KDIGO. Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney int. suppl. 2013,3(1):1–160.
Visseren FL.J., Mach F., Smulders YM, Carballo D., Koskinas K.C., Bäck M., et al ; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021;42(34):3227–37. https://doi.org/10.1093/eurheartj/ehab484
Stenvinkel P, Heimburger O, Paultre F, Diczfalusy U, Wang T, Berglund L, et al. Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure. Kidney Int 1999;55(5):1899–1991.
World Health Organization. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. 2011, World Health Organization. https://apps.who.int/iris/handle/10665/85839
Kerola T, Kauppi J, Sares-Jäske L, Anttonen O, Junttila MJ, Huikuri HV et al. Long-term prognostic impact of hyperuricemia in community. Scand J Clin Lab Invest, 2019. 79(3):148–53.
Longo-Mbenza B, Ngoma DV, Nahimana D, Mayuku DM, Fuele SM, Ekwanzala F, Beya C. Screen detection and the WHO stepwise approach to the prevalence and risk factors of arterial hypertension in Kinshasa. Eur J Cardiovasc Prev Rehabil. 2008 Oct;15(5):503-8. doi: 10.1097/HJR.0b013e3282f21640. PMID: 18830083
Blaise Makoso Nimi, Francois Lepira Bompeka, Benjamin Longo Mbenza, Carine Nkembi Nzuzi, Gédeon Longo Longo, Aliocha Nkodila, Roland Vangu Vangu, Memoria Makoso Nimi, Jean Pierre Mvuezolo Ndenga, Bienvenu Nkongo, Jean Paul Nkambu Nlandu, Deo Tagize, Antoinette Ndele Nzita, Michel Lutete Nkelani, Jean René M’Buyamba-Kabangu. Prevalence, Awareness, Treatment and Control of Hypertension Among Adults Living in the Port City of Boma, Democratic Republic of the Congo, European Journal of Clinical and Biomedical Sciences. Volume 7, Issue 1, February 2021 , pp. 12-20. doi: 10.11648/j.ejcbs.20210701.13.
Mupepe DM, Kayembe JM.N. Nkodila AN, Lupenzi BM, Samafundu YM, and Kintoki EV. Hypertension and associated cardiovascular risk factors among candidates enrolled at Kinshasa University for the academic year 2018-2019. Ann Afr Med 2020;2(13):e3575–83.
Garcia M., Mulvagh S.L., Merz C.N., Buring J.E., and Manson J.E. Cardiovascular disease in women: Clinical perspectives. Circ Res 2016;118 (8):1273–1293. doi: 10.1161/CIRCRESAHA.116.307547.
A Race Against Time: the challenge of cardiovascular disease in developing economies, Columbia University's Earth Institute on April 26, 2004. http://www.earth.columbia.edu/news/2004/st ory04-06b-04.htlm
Walker RW, McLarty DG, Kitange HM, Whiting D, Masuki G, Mtasiwa DM, et al. Stroke mortality in urban and rural Tanzania adult morbidity and mortality project. Lancet. 2000; 355(9216):1684–1687
Bayauli PM, M’Buyamba-Kayamba JJ, Lemogoum D, Thijs L, Dramaix M, Fagard R, et al. Cardiovascular risk factors among the inhabitants of an urban Congolese community: results of the vitaraa study. Int J Cardiol Metab Endocrine 2014;4:33–38.
Kassem K, Froguel P., and Wolowczuk I. Adipose tissue in Obesity-Related inflammation and insulin resistance: cells, cytokines, and chemokines. ISRN Inflamm 2013; 2013:139239.doi: 10.1155/2013/139239
Un Jung J., sook Cho M. Obesity and its metabolic complications: the Role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014; 15(4):6184–223.
Riccardi G, Rivellese AA. Dietary treatment of the metabolic syndrome, the optimal diet. Br J Nutr. 2000; 83(1):S143–S148.
Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu SM, Solomon CG, Willett WC. Diet, lifestyle and the risk of type II diabetes mellitus in women. N Engl J Med. 2001;345(11):790–797. =29
Ambrose JA, Barua RS. The pathophysiology of cigarette smoking and cardiovascular disease. J Am Coll Cardiol 2004;43(10):1731–37.
Dong R, Chen J, Zheng J, Zhang M, Zhang H, Wu M, et al. The role of oxidative stress in cardiometabolic risk related to ohtalate exposure in elderly diabetic patients from Shanghai. Environ Int. 2018;121:340–48. =31
Rajendran P, Rengarajan T, Thangavel J, Nishigaki Y, Sakthisekaran D, Sethi G, et al. The vascular endothelium and human diseases. Int J biol Sci 2013; 9(10):1057–69.
G Huet , J L Lemesre, G Grard, F Noireau, F Boutignon, M C Dieu et al. Serum lipid and lipoprotein abnormalities in human African trypanosomiasis. Trans R Soc Trop Med Hyg 1990; 84 (6): 792–4.
Lamour SD, Gomez-Romero M, Vorkas PA, Alibu VP, Saric J, Holme E et al. Discovery of infection associated metabolic markers in Human African Trypanosomiasis. PLoS Negl Trop Dis 2015; 9(10):e0004200.
Freedman BI, Murea M. Target organ damage in African American hypertension: role of APOL1. Curr Hypertens Rep. 2012;14(1):21–8. [PubMed: 22068337]).
Ito K, Bick AG, Flannick J, Friedman DJ, Genovese G, Parfenov MG, et al. Increased burden of cardiovascular disease in carriers of APOL1 genetic variants. Circ Res. 2014; 114(5):845–50.
McLean NO, Robinson TW, Freedman BI. APOL1 gene kidney risk variants and cardiovascular disease: getting to the heart of the matter. Am J Kidney Dis. 2017;70(2):281–89. doi:10.1053/j.ajkd.2016.11.020.
Langefeld CD, Divers J, Pajewski NM, Hawfield AT, Reboussin DM, Bild DE, et al.. Apolipoprotein L1 gene variants associate with prevalent kidney but not prevalent cardiovascular disease in the Systolic Blood Pressure Intervention Trial. Kidney Int. 2015;87(1):169–75. [PubMed: 25029429]
Nishimura K, Murakami T, Sakurai T, Miyoshi M, Kurahashi K, Kishi S, et al. Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism. Sci Rep. 2019;9(1):14869. doi: 10.1038/s41598-019-51367-7.
Gutiérrez OM, Irvin MR, Chaudhary NS, Cushman M, Zakai NA, David VA,et al. APOL1 nephropathy risk variants and incident cardio-vascular disease events in community-dwelling black adults. Circ Genom Precis Med. 2018; 11(6):e002098. doi: 10.1161/CIRCGEN.117.002098.
Howard VJ, Cushman M, Pulley L, Gomez CR, Go RC, Prineas RJ, et al. The reasons for geographic and racial differences in stroke study: Objectives and design. Neuroepidemiology. 2005; 25(3):135–143. doi: 10.1159/000086678
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Dominique M. Mupepe, Pascal M. Bayauli, Nathan B. Buila, Hippolyte N. Situakibanza, Pépé M. Ekulu, Marie-Noelle N.L. Wameso, Agathe B. Nkoy, Armand P. Okamba, Victoire A. Bikoumou, Kevin L. Karume, Lambertus P. Van den Heuvel, Elena N. Levtchenko, Dieudonné N. Mumba, Jean René M’Buyamba – Kabangu
This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution (CC-BY) 4.0 License that allows others to share the work with an acknowledgment of the work’s authorship and initial publication in this journal.
