Association between APOL 1 Risk Genotypes and Left Ventricular Hypertrophy among Sub-Saharan Africans in Trypanosoma Brucei Gambiense Endemic Rural Area
DOI:
https://doi.org/10.47941/ijhmnp.1948Keywords:
APOL1, LVH, Trypanosomiasis Endemic Area, DRCAbstract
Purpose. The relationship between APOL1 variants and cardiovascular disease remains controversial, thus, this study assessed the association between APOL1 high-risk genotypes and left ventricular hypertrophy (LVH) among sub-Saharan African in T.b. gambiense endemic area.
Methodology. We enrolled 238 subjects living in the region of Masimanimba, an endemic area of T.b.gambiense HAT. We evaluated the association between LVH on echocardiography and the status of APOL1 genes in participants with or without HAT. APOL1 high-risk genotype (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. 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 LVH. Odds ratios were provided with their 95% confidence intervals (Cis). Statistical significance was set at p < 0.05, based on 2-tailed test.
Findings. The prevalence of LVH (31.5%) increased with age and was similar in HAT-infected and non-infected subjects (29.8% vs. 32.6%; p=0.376). The trend of a greater left ventricular mass in participants with LVH carrying APOL1 HRG compared to those with LRG was not statistically significant (141g/m2 vs. 125 g/m2; p = 0.253). The frequency of HRG among participants with LVH was similar between HAT-infected and non-infected (15.8% vs. 9.1%; p = 0.806). Age ≥ 38 years [OR 2.5 (95% CI: 1.4-4.5), p = 0.001], hypertension [OR 2.4 (95% CI: 1.1-5.3), p = 0.034], WHR > 0.5 [OR 2.0 (95% CI: 1.0-3.6), p = 0.018] and CKD [OR 1.7 (95% CI: 1.0-3.0), p = 0.049] were associated with LVH. In multivariable logistic regression analysis age ≥ 38 years was the only independent determinant of LVH [ORa 2.0 (95% CI: 1.1-3.8), p = 0.020].
Unique contribution to theory, practice and policy. An assessment of cardiovascular risk is essential for individuals with LVH carrying APOL1 HRG in order to benefit from early and appropriate medical intervention. Further larger prospective follow-up survey is required to assess the incidence of LVH in individuals with APOL1 HRG variants.
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Atta MG , Estrella M.M, Kuperman M, Foy M.C, Fine DM, Racusen L.C, et al. HIV-Associated nephropathy patients with and without apolipoprotein L1 gene variants have similar clinical and histological characteristics. Kidney Int. 2012; 82(3): 338 - 43.
Genovese G., Friedman D.J., Ross M.D., Lecordier L., Uzureau P., Freedman B.I., et al. Association of Trypanolytic ApoL1 Variants with Kidney Disease in African Americans. Science 2010. 329 (5993): 841-845.
Friedman DJ and Pollak MR. Genetics of kidney failure and the evolving story of apol1. J Clin Invest. 2011; 121(9):3367-74.
Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P. et al. APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy. J Am Soc Nephrol 2011; 22 (11): 2129-2137.
Tzur S, Rosset S, Shemer R, Yudkovsky G, Selig S, Tarekegn A et al. Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene. Hum Genet. 2010; 128:345-350.
Larsen CP, Beggs ML, Saeed M, Walker PD. Apolipoprotein L1 risk variants associate with systemic lupus erythematosus-associated collapsing glomerulopathy. J Am Soc Nephrol. 2013; 24 (5):722-725.
Ashley-Koch AE, Okocha EC, Garrett ME, Soldano K., De Castro LM, Jonassaint JC et al. MYH9 and APOL1 are both associated with sickle cell disease nephropathy. Br J Haematol. 2011; 155 (3):386-394.
Freedman BI, Langefeld CD, Andringa KK, Croker JA, Williams AH, Garner NE, et al. End-stage kidney disease in African Americans with lupus nephritis associates with APOL1. Arthritis Rheumatol 2014; 66(2):390-6. doi: 10.1002/art.38220.
Tayo BO, Kramer H, Salako BL,Omri Gottesman, Colin A McKenzie, Adesola Ogunniyi, et al. Genetic variation in APOL1 and MYH9 genes is associated with chronic kidney disease among Nigerians. Int Urol Nephrol. 2013, 45(2): 485-94.
Ulasi II, Tzur S, Wasser WG, Shemer R, Kruzel E, Feigin E, et al. High population frequencies of APOL1 risk variants are associated with increased prevalence of non-diabetic chronic kidney disease in the Igbo people from south-eastern Nigeria. Nephron Clin Pract. 2013; 123(1-2):123-8. doi: 10.1159/000353223. Epub 2013 Jul 13. PMID: 23860441
McLean N.O, Robinson T.W, Freedman B.I. APOL1 Gene Kidney Risk Variants and Cardiovascular Disease: Getting to the Heart of the Matter. Am J Kidney Dis. 2017; 70(2): 281-289. doi:10.1053/j.ajkd.2016.11.020
Reiner AP, Susztak K. APOL1 Variants: From Parasites to Kidney Function to Cardiovascular Disease. Arterioscler Thromb Vasc Biol. 2016; 36(2):219-220. [PubMed: 26819463]
Farrall M. Cardiovascular twist to the rapidly evolving apolipoprotein L1 story. Circ Res. 2014; 114(5):746-747. [PubMed: 24577959]
Lipkowitz MS. Apolipoprotein L1: from obscurity to consistency to controversy. Kidney Int 2015; 87: 14-17.
KDIGO. Clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int. Suppl. 2013, 3(1): 1 - 160.
Lang RM, Badano LP , Mor-Avi V , Afilalo J , Armstrong A, Ernande L, et al., Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging, 2015. 16(3): p. 233-70
Varagic J, Susic D, Frolich E. Heart, aging and hypertension. Curr Opin Cardiol. 2001, 16: 336-41.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JJ et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003; 289:2560-2572.
Resnick HE, Lindsay RS, McDermott MM, Devereux RB, Jones KL, Fabsitz RR et al. Relationship of high and low ankle brachial index to all-cause and cardiovascular disease mortality: the Strong Heart Study. Circulation. 2004; 109(6):733-9. doi: 10.1161/01.CIR.0000112642.63927.54. PMID: 14970108.
Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA 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: 247-69
Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al; ESC National Cardiac Societies; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021; 42(34):3227-3337. doi: 10.1093/eurheartj/ehab484. Erratum in: Eur Heart J. 2022 Nov 7;43(42):4468. PMID: 34458905.
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: 1899-911.
World Health Organization"Ž. 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): p. 148-153.
Cooper A, Ilboudo H, Alibu VP, Ravel S, Enyaru J, Weir W et al. APOL1 renal risk variants have contrasting resistance and susceptibility associations with African trypanosomiasis. Elife. 2017; 6:e25461. doi: 10.7554/eLife.25461. PMID: 28537557; PMCID: PMC5495568.
Mulvany MJ, Baumbach GL, Aalkjaer C, Heagerty AM, Korsgaard N, Schiffrin EL, et al.. Vascular remodeling. Hypertension. 1996; 28(3):505-6. PMID: 8794840.
Boutouyrie P, Laurent S, Girerd X, Benetos A, Lacolley P, Abergel E et al.. Common carotid artery stiffness and patterns of left ventricular hypertrophy in hypertensive patients. Hypertension. 1995; 25(4 Pt 1):651-9. doi: 10.1161/01.hyp.25.4.651. PMID: 7721411.
Bussy C, Boutouyrie P, Lacolley P, Challande P, Laurent S. Intrinsic stiffness of the carotid arterial wall material in essential hypertensives. Hypertension. 2000; 35(5):1049-54. doi: 10.1161/01.hyp.35.5.1049. PMID: 10818063.
Boutouyrie P, Bussy C, Lacolley P, Girerd X, Laloux B, et al. Association between local pulse pressure, mean blood pressure, and large-artery remodeling. Circulation. 1999;100(13):1387-93. doi: 10.1161/01.cir.100.13.1387. PMID: 10500038
Cuspidi C, Mancia G, Ambrosioni E, Pessina A, Trimarco B, Zanchetti A; APROS Investigators. Left ventricular and carotid structure in untreated, uncomplicated essential hypertension: results from the Assessment Prognostic Risk Observational Survey (APROS). J Hum Hypertens. 2004;18(12):891-6. doi: 10.1038/sj.jhh.1001759. PMID: 15284833.
Mancia G, Carugo S, Grassi G, Lanzarotti A, Schiavina R, Cesana G, et al; Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) Study. Prevalence of left ventricular hypertrophy in hypertensive patients without and with blood pressure control: data from the PAMELA population. Pressioni Arteriose Monitorate E Loro Associazioni. Hypertension. 2002;39(3):744-9. doi: 10.1161/hy0302.104669. PMID: 11897756.
Langefeld CD, Divers J, Pajewski NM, Hawfield AT, Reboussin DM, Bild DE, et al; Systolic Blood Pressure Intervention Trial (SPRINT). 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. doi: 10.1038/ki.2014.254. Epub 2014 Jul 16. PMID: 25029429; PMCID: PMC4281289.
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. doi: 10.1161/CIRCRESAHA.114.302347. Epub 2013 Dec 30. PMID: 24379297; PMCID: PMC3982584.
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): 1564-1574. doi: 10.1016/j.jacc.2017.01.040
Freedman BI, Murea M. Target organ damage in African American hypertension: role of APOL1. Curr Hypertens Rep. 2012; 14:21-8. [PubMed: 22068337]).
Wannamethee SG, Shaper AG, Perry IJ. Serum creatinine concentration and risk of cardiovascular disease: a possible marker for increased risk of stroke. Stroke. 1997;28(3):557-63. doi: 10.1161/01.str.28.3.557. PMID: 9056611.
McCullough PA, Jurkovitz CT, Pergola PE, McGill JB, Brown WW, Collins AJ, et al, for the KEEP Investigators. Independent Components of Chronic Kidney Disease as a Cardiovascular Risk State: Results From the Kidney Early Evaluation Program (KEEP). Arch. Intern. Med. 2007; 167(11):1122-1129. [PubMed: 17563019].
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.
Gutirrez OM, Limou S, Lin F, Peralta CA, Kramer HJ, Carr JJ et al. APOL1 nephropathy risk variants do not associate with subclinical atherosclerosis or left ventricular mass in middle-aged black adults. Kidney Int. 2018;93:727-732. doi: 10.1016/j.kint.2017.08.019
Mann JF, Gerstein HC, Pogue J, Bosch J, Yusuf S. Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial. Ann Intern Med. 2001; 134(8):629-636. [PubMed: 11304102]
Pollak MR, Genovese G, Friedman DJ. APOL1 and kidney disease. Curr Opin Nephrol Hypertens. 2012; 21 (2):179-182.
Kruzel-Davila E, Walter GW, Aviram S, Skorecki K. APOL1 nephropathy: from gene to mechanisms of kidney injury. Nephrol Dial Transplant 2016; 31 (3): 349-358 doi: 10.1093/ndt/gfu391.
Gutirrez OM, Irvin MR, Ninad S. 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: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;25:135- 143. doi: 10.1159/000086678
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Copyright (c) 2024 Dominique M. Mupepe, Nathan B. Buila, Hippolyte N. Situakibanza, Pp M. Ekulu, Marie-Noelle N.L. Wameso, Agathe B. Nkoy, Exode S. Nsimba , Victoire A. Bikoumou , Kevin L. Karume, Jean Marie N. Kayembe , Lambertus P. Van den Heuvel , Elena N. Levtchenko , Eleuthère V. Kintoki , Benjamin M. Longo , Dieudonn N. Mumba , Jean Ren M'Buyamba - Kabangu
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