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7 - A Glimpse into Pharmacogenomics in Africa

Published online by Cambridge University Press:  02 December 2019

By
Collet Dandara  and
Alice Matimba
Edited by
Muntaser E. Ibrahim  and
Charles N. Rotimi
Muntaser E. Ibrahim
Affiliation:
University of Khartoum
Charles N. Rotimi
Affiliation:
National Human Genome Research Institute/NIH
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Summary

Interindividual and interpopulation differences may be used to guide and optimize disease treatment based on genetics and this is referred to as pharmacogenetics or pharmacogenomics. Pharmacogenetics is a branch of pharmacology that focuses on how single to few genetic markers affect drug efficacy and safety. Pharmacogenetics evaluates the effects of genetic variations on drug absorption, distribution, metabolism, and excretion (ADME), thereby broadly affecting its pharmacokinetic (PK) and pharmacodynamic (PD) properties (Hansen et al. 2009; Kitzmiller et al. 2011; Malik et al. 2010). Pharmacogenomics, on the other hand, is the study of how the variation across the whole genome influences response to therapeutic drugs and encompasses genes affecting host susceptibility to disease as well as disease pathways and mechanisms that affect gene expression and function. Both terms may be used interchangeably and will be referred to as pharmacogenomics in this chapter.

Type
Chapter
Information
The Genetics of African Populations in Health and Disease , pp. 128 - 167
Publisher: Cambridge University Press
Print publication year: 2019

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References

Abdissa, SG, Fekade, D, Feleke, Y, Seboxa, T, and Diro, E (2012). Adverse drug reactions associated with antiretroviral treatment among adult Ethiopian patients in a tertiary hospital. Ethiop Med J 50(2): 107–113.Google Scholar
Ahmed, S, Zhou, Z, Zhou, J, and Chen, SQ (2016). Pharmacogenomics of drug metabolizing enzymes and transporters: relevance to precision medicine. Genomics Proteomics Bioinformatics 14(5): 298–313.CrossRefGoogle ScholarPubMed
Akinboro, AO, Akinyemi, SO, Olaitan, PB, et al. (2014). Quality of life of Nigerians living with human immunodeficiency virus. Pan Afr Med J 18: 234.Google Scholar
Aklillu, E, Herrlin, K, Gustafsson, LL, Bertilsson, L, and Ingelman-Sundberg, M (2002). Evidence for environmental influence on CYP2D6-catalysed debrisoquine hydroxylation as demonstrated by phenotyping and genotyping of Ethiopians living in Ethiopia or in Sweden. Pharmacogenetics 12(5): 375–383.Google Scholar
Anderson, T, Nkhoma, S, Ecker, A, and Fidock, D (2011). How can we identify parasite genes that underlie antimalarial drug resistance? Pharmacogenomics 12(1): 59–85.Google Scholar
Aneni, EC, Hamer, DH, and Gill, CJ (2013). Systematic review of current and emerging strategies for reducing morbidity from malaria in sickle cell disease. Trop Med Int Health 18: 313–327.Google Scholar
Angamo, MT, Curtain, CM, Chalmers, L, Yilma, D, and Bereznicki, L (2017). Predictors of adverse drug reaction-related hospitalization in Southwest Ethiopia: a prospective cross-sectional study. PLoS One 12(10): e0186631.Google Scholar
Ankathil, R (2017). ABCB1 genetic variants in leukemias: current insights into treatment outcomes. Pharmgenomics Pers Med 10: 169–181.Google Scholar
Apinjoh, TO, Mugri, RN, Miotto, O, et al. (2017). Molecular markers for artemisinin and partner drug resistance in natural Plasmodium falciparum populations following increased insecticide treated net coverage along the slope of mount Cameroon: cross-sectional study. Infect Dis Poverty 6(1): 136.Google Scholar
Arts, EJ and Hazuda, DJ (2012). HIV-1 antiretroviral drug therapy. Cold Spring Harb Perspect Med 2: a007161.Google Scholar
Atun, R, Davies, JI, Gale, EAM, et al. (2017). Diabetes in sub-Saharan Africa: from clinical care to health policy. Lancet Diabetes Endocrinol 5(8): 622–667.Google Scholar
Azuma, J, Ohno, M, Kubota, R, et al. (2013). Pharmacogenetics-based tuberculosis therapy research group. NAT2 genotype guided regimen reduces isoniazid induced liver injury and early treatment failure in the 6-month four-drug standard treatment of tuberculosis: a randomized controlled trial for pharmacogenetics-based therapy. Eur J Clin Pharmacol 69(5): 1091–1101.CrossRefGoogle Scholar
Bader, LA and Elewa, H (2016). The impact of genetic and non-genetic factors on warfarin dose prediction in MENA region: a systematic review. PLoS One 11(12): e0168732.CrossRefGoogle ScholarPubMed
Bains, RK, Kovacevic, M, Plaster, CA, et al. (2013). Molecular diversity and population structure at the Cytochrome P450 3A5 gene in Africa. BMC Genet 14: 34.Google Scholar
Baker, JL, Shriner, D, Bentley, AR, and Rotimi, CN (2017). Pharmacogenomic implications of the evolutionary history of infectious diseases in Africa. Pharmacogenomics J 17(2): 112–120.Google Scholar
Bapiro, TE, Hasler, JA, Ridderstrom, M, and Masimirembwa, CM (2002). The molecular and enzyme kinetic basis for the diminished activity of the cytochrome P450 2D6.17 (CYP2D6.17) variant: potential implications for CYP2D6 phenotyping studies and the clinical use of CYP2D6 substrate drugs in some African populations. Biochem Pharmacol 64: 1387–1398.Google Scholar
Becker, ML, Visser, LE, Van Schaik, RH, et al. (2009). Genetic variation in the multidrug and toxin extrusion 1 transporter protein influences the glucose-lowering effect of metformin in patients with diabetes: a preliminary study. Diabetes 58: 745–749.Google Scholar
Beutler, E, Dern, RJ, and Alving, AS (1955). The hemolytic effect of primaquine: VI. An in vitro test for sensitivity of erythrocytes to primaquine. J Lab Clin Med 45: 40–50.Google Scholar
Bretscher, MT, Griffin, JT, Ghani, AC, and Okell, LC (2017). Modelling the benefits of long-acting or transmission-blocking drugs for reducing Plasmodium falciparum transmission by case management or by mass treatment. Malar J 16(1): 341.Google Scholar
Bringolf, L, Pestalozzi, B, Fink, D, and Dedes, K (2017). Exploring prognostic factors for HER2-positive metastatic breast cancer: a retrospective cohort study in a major Swiss hospital. Swiss Med Wkly 146: w14393.Google Scholar
Brousseau, DC, Mccarver, DG, Drendel, AL, Divakaran, K, and Panepinto, JA (2007). The effect of CYP2D6 polymorphisms on the response to pain treatment for pediatric sickle cell pain crisis. J Pediatr 150: 623–626.Google Scholar
Byakika-Kibwika, P, Lamorde, M, Mayito, J, et al. (2012). Significant pharmacokinetic interactions between artemether/lumefantrine and efavirenz or nevirapine in HIV-infected Ugandan adults. J Antimicrob Chemother 67: 2213–2221.Google Scholar
Canestaro, WJ, Brooks, DG, Chaplin, D, et al. (2012). Statin pharmacogenomics: opportunities to improve patient outcomes and healthcare costs with genetic testing. J Pers Med 2: 158–174.Google Scholar
Carr, DF, Chaponda, M, Cornejo Castro, EM, et al. (2014). CYP2B6 c.983T>C polymorphism is associated with nevirapine hypersensitivity in Malawian and Ugandan HIV populations. J Antimicrob Chemother 69: 3329–3334.Google Scholar
Carr, DF, Bourgeois, S, Chaponda, M, et al. (2017). Genome-wide association study of nevirapine hypersensitivity in a sub-Saharan African HIV-infected population. J Antimicrob Chemother 72(4): 1152–1162.Google Scholar
Caudle, KE, Klein, TE, Hoffman, JM, et al. (2014). Incorporation of pharmacogenomics into routine clinical practice: the Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline development process. Curr Drug Metab 15(2): 209–217.Google Scholar
Chandra, R (2017). The role of pharmacogenomics in precision medicine. Med Lab Obs 49(9): 8–14.Google Scholar
Charache, S, Terrin, ML, Moore, RD, et al. (1995). Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia: investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. N Engl J Med 332: 1317–1322.Google Scholar
Chigutsa, E, Visser, ME, Swart, EC, et al. (2011). The SLCO1B1 rs4149032 polymorphism is highly prevalent in South Africans and is associated with reduced rifampin concentrations: dosing implications. Antimicrob Agents Chemother 55(9): 4122–4127.Google Scholar
Choudhury, A, Ramsay, M, Hazelhurst, S, et al. (2017). Whole-genome sequencing for an enhanced understanding of genetic variation among South Africans. Nat Commun 8(1): 2062.CrossRefGoogle ScholarPubMed
Collins, SL, Carr, DF, Pirmohamed, M (2016). Advances in the pharmacogenomics of adverse drug reactions. Drug Saf 39(1): 15–27.Google Scholar
Conrad, MD, Mota, D, Musiime, A, et al. (2017). Comparative prevalence of Plasmodium falciparum resistance-associated genetic polymorphisms in parasites infecting humans and mosquitoes in Uganda. Am J Trop Med Hyg 97(5): 1576–1580.Google Scholar
Crews, KR, Gaedigk, A, Dunnenberger, HM, et al. (2014). Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update. Clin Pharmacol Ther 95(4): 376–382.Google Scholar
Crews, KR, Caudle, KE, Dunnenberger, HM, Sadhasivam, S, and Skaar, TC (2015). Considerations for the utility of the CPIC guideline for CYP2D6 genotype and codeine therapy. Clin Chem 61(5): 775–776.Google Scholar
Daka, A, Dimovski, A, Kapedanovska, A, et al. (2015). Effects of single nucleotide polymorphisms and haplotypes of the SLCO1B1 gene on the pharmacokinetic profile of atorvastatin in healthy Macedonian volunteers. Pharmazie 70(7): 480–488.Google ScholarPubMed
Dandara, C, Basvi, PT, Bapiro, TE, Sayi, J, and Hasler, JA (2004). Frequency of -163 C>A and 63 C>G single nucleotide polymorphism of cytochrome P450 1A2 in two African populations. Clin Chem Lab Med 42: 939–941.Google Scholar
Dandara, C, Lombard, Z, Du Plooy, I, et al. (2011). Genetic variants in CYP (-1A2, -2C9, -2C19, -3A4 and -3A5), VKORC1 and ABCB1 genes in a black South African population: a window into diversity. Pharmacogenomics 12(12): 1663–1670.Google Scholar
Dandara, C, Swart, M, Mpeta, B, Wonkam, A, and Masimirembwa, C (2014). Cytochrome P450 pharmacogenetics in African populations: implications for public health. Expert Opin Drug Metab Toxicol 10: 769–785.Google Scholar
Dandara, C, Suarez-Kurtz, G, and Aklillu, E (2016). Conference report: first Pharmacogenetics and Precision Medicine Conference in Africa (April 7–9, 2016, Cape Town, South Africa). OMICS 20(9): 496–497.Google Scholar
Daneshjou, R, Gamazon, ER, Burkley, B, et al. (2014). Genetic variant in folate homeostasis is associated with lower warfarin dose in African Americans. Blood 124(14): 2298–2305.Google Scholar
Dang, MT, Hambleton, J, and Kayser, SR (2005). The influence of ethnicity on warfarin dosage requirement. Ann Pharmacother 39: 1008–1012.Google Scholar
Darbari, DS, Minniti, CP, Rana, S, and Van Den Anker, J (2008a). Pharmacogenetics of morphine: potential implications in sickle cell disease. Am J Hematol 83: 233–236.Google Scholar
Darbari, DS, Van Schaik, RH, Capparelli, EV, et al. (2008b). UGT2B7 promoter variant -840G>A contributes to the variability in hepatic clearance of morphine in patients with sickle cell disease. Am J Hematol 83: 200–202.Google Scholar
den Dunnen, JT, Dalgleish, R, Maglott, DR, et al. (2016). HGVS recommendations for the description of sequence variants: 2016 update. Hum Mutat 37(6): 564–569.CrossRefGoogle ScholarPubMed
Deng, J, Vozmediano, V, Rodriguez, M, Cavallari, LH, and Schmidt, S (2017). Genotype-guided dosing of warfarin through modeling and simulation. Eur J Pharm Sci 109S: S9–S14.Google Scholar
Dhoro, M, Zvada, S, Ngara, B, et al. (2015). CYP2B6*6, CYP2B6*18, body weight and sex are predictors of efavirenz pharmacokinetics and treatment response: population pharmacokinetic modeling in an HIV/AIDS and TB cohort in Zimbabwe. BMC Pharmacol Toxicol 27(16): 4.Google Scholar
Diop, S, Soudre, F, Seck, M, et al. (2011). Sickle-cell disease and malaria: evaluation of seasonal intermittent preventive treatment with sulfadoxine-pyrimethamine in Senegalese patients: a randomized placebo-controlled trial. Ann Hematol 90: 23–27.Google Scholar
Dooley, KE, Flexner, C, and Andrade, AS (2008). Drug interactions involving combination antiretroviral therapy and other anti-infective agents: repercussions for resource-limited countries. J Infect Dis 198: 948–961.Google Scholar
Dujic, T, Zhou, K, Donnelly, LA, et al. (2015). Association of organic cation transporter 1 with intolerance to metformin in type 2 diabetes: a GoDARTS study. Diabetes 64: 1786–1793.Google Scholar
Dujic, T, Zhou, K, Donnelly, LA, et al. (2018). Interaction between variants in the CYP2C9 and POR genes and the risk of sulfonylurea-induced hypoglycaemia: a GoDARTS study. Diabetes Obes Metab 20(1): 211–214.Google Scholar
Eke, FU and Anochie, I (2003). Effects of pyrimethamine versus proguanil in malarial chemoprophylaxis in children with sickle cell disease: a randomized, placebo-controlled, open-label study. Curr Ther Res Clin Exp 64: 616–625.CrossRefGoogle ScholarPubMed
Eluwa, GI, Badru, T, Agu, KA, et al. (2012). Adverse drug reactions to antiretroviral therapy (ARVs): incidence, type and risk factors in Nigeria. BMC Clin Pharmacol 12: 7.Google Scholar
Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group (2013). Recommendations from the EGAPP Working Group: can testing of tumor tissue for mutations in EGFR pathway downstream effector genes in patients with metastatic colorectal cancer improve health outcomes by guiding decisions regarding anti-EGFR therapy? Genet Med 15(7): 517–527.Google Scholar
Floyd, JS and Psaty, BM (2016). The application of genomics in diabetes: barriers to discovery and implementation. Diabetes Care 39(11): 1858–1869.Google Scholar
Fohner, A, Muzquiz, LI, Austin, MA, et al. (2013). Pharmacogenetics in American Indian populations: analysis of CYP2D6, CYP3A4, CYP3A5, and CYP2C9 in the Confederated Salish and Kootenai Tribes. Pharmacogenet Genomics 23: 403–414.Google Scholar
Fricke-Galindo, I, Céspedes-Garro, C, Rodrigues-Soares, F, et al. (2016). Interethnic variation of CYP2C19 alleles, “predicted” phenotypes and “measured” metabolic phenotypes across world populations. Pharmacogenomics J 16(2): 113–123.CrossRefGoogle ScholarPubMed
Gaedigk, A, Blum, M, Gaedigk, R, Eichelbaum, M, and Meyer, UA (1991). Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism. Am J Hum Genet 48(5): 943–950.Google Scholar
Gaedigk, A, Simon, SD, Pearce, RE, et al. (2008). The CYP2D6 activity score: translating genotype information into a qualitative measure of phenotype. Clin Pharmacol Ther 83: 234–242.Google Scholar
Gaedigk, A, Ingelman-Sundberg, M, Miller, NA, et al. (2017a). The Pharmacogene Variation (PharmVar) Consortium: incorporation of the human cytochrome P450 (CYP) allele nomenclature database. Clin Pharmacol Ther. DOI: 10.1002/cpt.910.Google Scholar
Gaedigk, A, Sangkuhl, K, Whirl-Carrillo, M, Klein, T, and Leeder, JS (2017b). Prediction of CYP2D6 phenotype from genotype across world populations. Genet Med 19(1): 69–76.Google Scholar
Ganesh, SK, Arnett, DK, Assimes, TL, et al. (2013). Genetics and genomics for the prevention and treatment of cardiovascular disease: update – a scientific statement from the American Heart Association. Circulation 128: 2813–2851.Google Scholar
Gelissen, IC and Brown, AJ (2012). Predicting response to statins by pharmacogenetic testing. Pharmacogenomics 13: 1223–1225.Google Scholar
Gounden, V, Van Niekerk, C, Snyman, T, and George, JA (2010). Presence of the CYP2B6 516G> T polymorphism, increased plasma efavirenz concentrations and early neuropsychiatric side effects in South African HIV-infected patients. AIDS Res Ther 7: 32.Google Scholar
Green, NS and Barral, S (2011). Genetic modifiers of HbF and response to hydroxyurea in sickle cell disease. Pediatr Blood Cancer 56: 177–181.Google Scholar
Grosse, SD, Odame, I, Atrash, HK, et al. (2011). Sickle cell disease in Africa: a neglected cause of early childhood mortality. Am J Prev Med 41: S398–S405.Google Scholar
Guo, Y, Shi, L, Hong, H, et al. (2013). Studies on abacavir-induced hypersensitivity reaction: a successful example of translation of pharmacogenetics to personalized medicine. Sci China Life Sci 56(2): 119–124.Google Scholar
Gupta, VH, Amarapurkar, DN, Singh, M, et al. (2013). Association of N-acetyltransferase 2 and cytochrome P450 2E1 gene polymorphisms with antituberculosis drug-induced hepatotoxicity in Western India. J Gastroenterol Hepatol 28: 1368–1374.Google Scholar
Gurdasani, D, Carstensen, T, Tekola-Ayele, F, et al. (2015). The African Genome Variation Project shapes medical genetics in Africa. Nature 517(7534): 327–332.Google Scholar
Hansen, NT, Brunak, S, and Altman, RB (2009). Generating genome-scale candidate gene lists for pharmacogenomics. Clin Pharmacol Ther 86: 183–189.Google Scholar
He, L, Vasiliou, K and Nebert, DW (2009). Analysis and update of the human solute carrier (SLC) gene superfamily. Hum Genomics 3(2): 195–206.Google Scholar
Helland, T, Henne, N, Bifulco, E, et al. (2017). Serum concentrations of active tamoxifen metabolites predict long-term survival in adjuvantly treated breast cancer patients. Breast Cancer Res 19(1): 125.Google Scholar
Hennig, S, Naiker, S, Reddy, T, et al. (2015). Effect of SLCO1B1 polymorphisms on rifabutin pharmacokinetics in African HIV-infected patients with tuberculosis. Antimicrob Agents Chemother 60(1): 617–620.Google Scholar
Hicks, JK, Swen, JJ, Thorn, CF, et al. (2013). Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants. Clin Pharmacol Ther 93: 402–408.Google Scholar
Holstein, A, Hahn, M, Korner, A, Stumvoll, M, and Kovacs, P (2011). TCF7L2 and therapeutic response to sulfonylureas in patients with type 2 diabetes. BMC Med Genet 12: 30.Google Scholar
Howes, RE, Piel, FB, Patil, AP, et al. (2012). G6PD deficiency prevalence and estimates of affected populations in malaria endemic countries: a geostatistical model-based map. PLoS Med 9(11): e1001339.Google Scholar
Hu, M and Tomlinson, B (2013). Pharmacogenomics of lipid-lowering therapies. Pharmacogenomics 14: 981–995.Google Scholar
Jaffar, S and Gill, G (2017). The crisis of diabetes in sub-Saharan Africa. Lancet Diabetes Endocrinol 5(8): 574–575.Google Scholar
Johansson, I and Ingelman-Sundberg, M (2008). Current research in drug metabolism, drug transport and drug development. Drug News Perspect 21(9): 518–528.Google Scholar
Joly, P, Gagnieu, MC, Bardel, C, et al. (2012). Genotypic screening of the main opiate-related polymorphisms in a cohort of 139 sickle cell disease patients. Am J Hematol 87: 534–536.Google Scholar
Jung, JA, Kim, TE, Lee, H, et al. (2015). A proposal for an individualized pharmacogenetic-guided isoniazid dosage regimen for patients with tuberculosis. Drug Des Devel Ther 9: 5433–5438. DOI: 10.2147/DDDT.S87131.Google Scholar
Kalman, LV, Agúndez, J, Appell, ML, et al. (2016). Pharmacogenetic allele nomenclature: international workgroup recommendations for test result reporting. Clin Pharmacol Ther 99(2): 172–185. DOI: 10.1002/cpt.280.Google Scholar
Kalow, W (1956). Familial incidence of low pseudocholinesterase level. Lancet 268: 576–577.Google Scholar
Kaye, JB, Schultz, LE, Steiner, HE, et al. (2017). Warfarin pharmacogenomics in diverse populations. Pharmacotherapy 37(9): 1150–1163.Google Scholar
Kharsany, AB and Karim, QA (2016). HIV infection and AIDS in sub-Saharan Africa: current status, challenges and opportunities. Open AIDS J 10: 34–48.Google Scholar
Kitzmiller, JP, Groen, DK, Phelps, MA, and Sadee, W (2011). Pharmacogenomic testing: relevance in medical practice – why drugs work in some patients but not in others. Cleve Clin J Med 78: 243–257.Google Scholar
Klein, K, Lang, T, Saussele, T, et al. (2005). Genetic variability of CYP2B6 in populations of African and Asian origin: allele frequencies, novel functional variants, and possible implications for anti-HIV therapy with efavirenz. Pharmacogenet Genomics 15(12): 861–873.Google Scholar
Kubo, K, Ohara, M, Tachikawa, M, et al. (2017). Population differences in S-warfarin pharmacokinetics among African Americans, Asians and whites: their influence on pharmacogenetic dosing algorithms. Pharmacogenomics J 17(6): 494–500.Google Scholar
Kudzi, W, Addy, BS, and Dzudzor, B (2015). Knowledge of pharmacogenetics among healthcare professionals and faculty members of health training institutions in Ghana. Ghana Med J 49(1): 50–56.Google Scholar
Lee, J, Wang, R, Yang, Y, et al. (2015). The effect of ABCB1 C3435T polymorphism on cyclosporine dose requirements in kidney transplant recipients: a meta-analysis. Basic Clin Pharmacol Toxicol 117(2): 117–125.Google Scholar
Lettre, G, Sankaran, VG, Bezerra, MA, et al. (2008). DNA polymorphisms at the BCL11A, HBS1L-MYB, and beta-globin loci associate with fetal hemoglobin levels and pain crises in sickle cell disease. PNAS 105: 11869–11874.Google Scholar
Lewthwaite, CJ (1962). A trial of chemoprophylaxis in sickle cell anaemia: preliminary communication. East Afr Med J 39: 196–199.Google ScholarPubMed
Li, J, Lao, X, Zhang, C, et al. (2014). Increased genetic diversity of ADME genes in African Americans compared with their putative ancestral source populations and implications for pharmacogenomics. BMC Genet 15: 52.Google Scholar
Li, Q, Tang, TT, Jiang, F, et al. (2017). Polymorphisms of the KCNQ1 gene are associated with the therapeutic responses of sulfonylureas in Chinese patients with type 2 diabetes. Acta Pharmacol Sin 38(1): 80–89.Google Scholar
Limdi, NA, Brown, TM, Yan, Q, et al. (2015). Race influences warfarin dose changes associated with genetic factors. Blood 126(4): 539–545.Google Scholar
Lynch, T and Price, A (2007). The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. Am Fam Physician 76(3): 391–396.Google Scholar
Maimbo, M, Kiyotani, K, Mushiroda, T, Masimirembwa, C, and Nakamura, Y (2012). CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV-infected Zimbabweans. Eur J Clin Pharmacol 68: 267–271.Google Scholar
Makani, J, Komba, AN, Cox, SE, et al. (2010). Malaria in patients with sickle cell anemia: burden, risk factors, and outcome at the outpatient clinic and during hospitalization. Blood 115: 215–220.Google Scholar
Makani, J, Ofori-Acquah, SF, Nnodu, O, Wonkam, A, and Ohene-Frempong, K (2013). Sickle cell disease: new opportunities and challenges in Africa. Sci World J 2013: 193252.Google Scholar
Malik, VS, Popkin, BM, Bray, GA, Despres, JP, and Hu, FB (2010). Sugar-sweetened beverages, obesity, type 2 diabetes mellitus, and cardiovascular disease risk. Circulation 121: 1356–1364.Google Scholar
Manjurano, A, Sepulveda, N, Nadjm, B, et al. (2015). African glucose-6-phosphate dehydrogenase alleles associated with protection from severe malaria in heterozygous females in Tanzania. PLoS Genet 11(2): e1004960.Google Scholar
Masenyetse, LJ, Manda, SO, and Mwambi, HG (2015). An assessment of adverse drug reactions among HIV positive patients receiving antiretroviral treatment in South Africa. AIDS Res Ther 12: 6.Google Scholar
Masimirembwa, C and Matimba, A (2012). Pharmacogenomics in Africa: diversity as an opportunity for personalized healthcare in genomics applications for the developing world. In Nelson, KE and Jones-Nelson, B, eds., Genomics Applications for the Developing World. Springer, pp. 161–181.Google Scholar
Masimirembwa, C, Persson, I, Bertilsson, L, Hasler, J, and Ingelman-Sundberg, M (1996). A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity. Br J Clin Pharmacol 42: 713–719.Google Scholar
Masimirembwa, C, Dandara, C, and Hasler, J (2014). Population diversity and pharmacogenomics in Africa. In Padmanabhan, S., ed., Handbook of Pharmacogenomics and Stratified Medicine. Academic Press, pp. 161–182.Google Scholar
Masimirembwa, C, Dandara, C, and Leutscher, PD (2016). Rolling out efavirenz for HIV precision medicine in Africa: are we ready for pharmacovigilance and tackling neuropsychiatric adverse effects? OMICS 20(10): 575–580.Google Scholar
Matimba, A, Oluka, MN, Ebeshi, BU, et al. (2008). Establishment of a biobank and pharmacogenetics database of African populations. Eur J Hum Genet 16(7): 780–783.Google Scholar
Matimba, A, Del-Favero, J, Van Broeckhoven, C, and Masimirembwa, C (2009). Novel variants of major drug-metabolising enzyme genes in diverse African populations and their predicted functional effects. Hum Genomics 3(2): 169–190.Google Scholar
Matimba, A, Dhoro, M, and Dandara, C (2016). Is there a role of pharmacogenomics in Africa? Glob Health Epidemiol Genom 1. DOI: 10.1017/gheg.2016.4.Google Scholar
Maxwell, RR and Cole, PD (2017). Pharmacogenetic predictors of treatment-related toxicity among children with acute lymphoblastic leukemia. Curr Hematol Malig Rep 12(3): 176–186.Google Scholar
McAuley, CF, Webb, C, Makani, J, et al. (2010). High mortality from Plasmodium falciparum malaria in children living with sickle cell anemia on the coast of Kenya. Blood 116: 1663–1668.Google Scholar
Meyer, ZU, Schwabedissen, HE, Albers, M, et al. (2015). Function-impairing polymorphisms of the hepatic uptake transporter SLCO1B1 modify the therapeutic efficacy of statins in a population-based cohort. Pharmacogenet Genomics 25(1): 8–18.Google Scholar
Mhandire, D, Lacerda, M, Castel, S, et al. (2015). Effects of CYP2B6 and CYP1A2 genetic variation on nevirapine plasma concentration and pharmacodynamics as measured by CD4 cell count in Zimbabwean HIV-infected patients. OMICS 19(9): 553–562.Google Scholar
Mitchell, C, Gregersen, N, and Krause, A (2011). Novel CYP2C9 and VKORC1 gene variants associated with warfarin dosage variability in the South African black population. Pharmacogenomics 12: 953–963.Google Scholar
Moaddeb, J and Haga, SB (2013). Pharmacogenetic testing: current evidence of clinical utility. Ther Adv Drug Saf 4(4): 155–169.Google Scholar
Modell, B and Darlison, M (2008). Global epidemiology of haemoglobin disorders and derived service indicators. Bull World Health Organ 86: 480–487.Google Scholar
Moriyama, T, Yang, YL, Nishii, R, et al. (2017). Novel variants in NUDT15 and thiopurine intolerance in children with acute lymphoblastic leukemia from diverse ancestry. Blood 130(10): 1209–1212.Google Scholar
Moss, DM, Liptrott, NJ, Siccardi, M, and Owen, A (2015). Interactions of antiretroviral drugs with the SLC22A1 (OCT1) drug transporter. Front Pharmacol 6: 78.Google Scholar
Moss, JA (2013). HIV/AIDS review. Radiol Technol 84(3): 247–267.Google Scholar
Mouton, JP, Njuguna, C, Kramer, N, et al. (2016). Adverse drug reactions causing admission to medical wards: a cross-sectional survey at 4 hospitals in South Africa. Medicine (Baltimore) 95(19): e3437.Google Scholar
Mpye, K, Matimba, A, Dzobo, K, et al. (2016). Disease burden and the role of pharmacogenomics in African populations. Glob Health Epidemiol Genom 2. DOI: 10.1017/gheg.2016.21.Google Scholar
Mtatiro, SN, Singh, T, Rooks, H, et al. (2014). Genome wide association study of fetal hemoglobin in sickle cell anemia in Tanzania. PLoS One 9: e111464.Google Scholar
Mtatiro, SN, Mgaya, J, Singh, T, et al. (2015). Genetic association of fetal-hemoglobin levels in individuals with sickle cell disease in Tanzania maps to conserved regulatory elements within the MYB core enhancer. BMC Med Genet 16: 4.Google Scholar
Mukonzo, JK, Okwera, A, Nakasujja, N, et al. (2013). Influence of efavirenz pharmacokinetics and pharmacogenetics on neuropsychological disorders in Ugandan HIV-positive patients with or without tuberculosis: a prospective cohort study. BMC Infect Dis 13: 261.Google Scholar
Mukonzo, JK, Owen, JS, Ogwal-Okeng, J, et al. (2014). Pharmacogenetic-based efavirenz dose modification: suggestions for an African population and the different CYP2B6 genotypes. PLoS One 9(1): e86919.Google Scholar
Mutabazi-Mwesigire, D, Seeley, J, Martin, F, and Katamba, A (2014). Perceptions of quality of life among Ugandan patients living with HIV: a qualitative study. BMC Public Health 10(14): 343.Google Scholar
Namme Luma, H, Doualla, MS, Choukem, SP, et al. (2012). Adverse drug reactions of highly active antiretroviral therapy (HAART) in HIV infected patients at the General Hospital, Douala, Cameroon: a cross sectional study. Pan Afr Med J 12: 87.Google Scholar
Ndefo, UA, Maxwell, AE, Nguyen, H, and Chiobi, TL (2008). Pharmacological management of sickle cell disease. Pharm Ther 33: 238–243.Google Scholar
Ngaimisi, E, Habtewold, A, Minzi, O, et al. (2013). Importance of ethnicity, CYP2B6 and ABCB1 genotype for efavirenz pharmacokinetics and treatment outcomes: a parallel-group prospective cohort study in two sub-Saharan Africa populations. PLoS One 8: e67946.Google Scholar
Nyakutira, C, Roshammar, D, Chigutsa, E, et al. (2008). High prevalence of the CYP2B6 516G-->T(*6) variant and effect on the population pharmacokinetics of efavirenz in HIV/AIDS outpatients in Zimbabwe. Eur J Clin Pharmacol 64: 357–365.Google Scholar
Nyirenda, MJ (2016). Non-communicable diseases in sub-Saharan Africa: understanding the drivers of the epidemic to inform intervention strategies. Int Health 8(3): 157–158.Google Scholar
Okwi, AL, Byarugaba, W, Ndugwa, CM, et al. (2010). An up-date on the prevalence of sickle cell trait in Eastern and Western Uganda. BMC Blood Disord 10: 5.Google Scholar
Oluka, MN, Okalebo, FA, Guantai, AN, Mcclelland, RS, and Graham, SM (2015). Cytochrome P450 2B6 genetic variants are associated with plasma nevirapine levels and clinical response in HIV-1 infected Kenyan women: a prospective cohort study. AIDS Res Ther 12: 10.Google Scholar
Ombeni, W and Kamuhabwa, AR (2016). Lipid profile in HIV-infected patients using first-line antiretroviral drugs. J Int Assoc Provid AIDS Care 15(2): 164–171.Google Scholar
Oniyangi, O and Omari, AA (2006). Malaria chemoprophylaxis in sickle cell disease. Cochrane Database Syst Rev 4: Cd003489.Google Scholar
Perera, MA, Cavallari, LH, Limdi, NA, et al. (2013). Genetic variants associated with warfarin dose in African-American individuals: a genome-wide association study. Lancet 382(9894): 790–796.Google Scholar
Pino, P, Taoufiq, Z, Brun, M, et al. (2006). Effects of hydroxyurea on malaria, parasite growth and adhesion in experimental models. Parasite Immunol 28: 675–680.Google Scholar
Pirmohamed, M, Burnside, G, Eriksson, N, et al. (2013). A randomized trial of genotype-guided dosing of warfarin. N Engl J Med 369(24): 2294–2303.Google Scholar
Preissner, SC, Hoffmann, MF, Preissner, R, et al. (2013). Polymorphic cytochrome P450 enzymes (CYPs) and their role in personalized therapy. PLoS One 8(12): e82562.Google Scholar
Price-Evans, DA, Manley, FA, and Mckusick, VA (1960). Genetic control of isoniazid metabolism in man. Br Med J 2: 485–491.Google Scholar
Rajman, I, Knapp, L, Morgan, T, and Masimirembwa, C (2017). African genetic diversity: implications for Cytochrome P450 mediated drug metabolism and drug development. EBioMedicine 17: 67–74.Google Scholar
Rasmussen, SA, Ceja, FG, Conrad, MD, et al. (2017). Changing antimalarial drug sensitivities in Uganda. Antimicrob Agents Chemother 61(12): e01516-17.Google Scholar
Relling, MV and Klein, TE (2011). CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin Pharmacol Ther 89(3): 464–467.Google Scholar
Relling, MV, Gardner, EE, Sandborn, WJ, et al. (2013). Clinical Pharmacogenetics Implementation Consortium Guidelines for thiopurine methyltransferase genotype and thiopurine dosing: 2013 update. Clin Pharmacol Ther. 93: 324–325.Google Scholar
Rendic, S and Guengerich, FP (2010). Update information on drug metabolism systems: 2009, part II – summary of information on the effects of diseases and environmental factors on human cytochrome P450 (CYP) enzymes and transporters. Curr Drug Metab 11(1): 4–84.Google Scholar
Robarge, JD, Li, L, Desta, Z, Nguyen, A, and Flockhart, DA (2007). The star-allele nomenclature: retooling for translational genomics. Clin Pharmacol Ther 82(3): 244–248.Google Scholar
Roden, DM, Wilke, RA, Kroemer, HK, and Stein, CM (2011). Pharmacogenomics: the genetics of variable drug responses. Circulation 123(15): 1661–1670.Google Scholar
Röhrich, CR, Drögemöller, BI, Ikediobi, O, et al. (2016). CYP2B6*6 and CYP2B6*18 predict long-term efavirenz: exposure measured in hair samples in HIV-positive South African women. AIDS Res Hum Retroviruses 32(6): 529–538.Google Scholar
Ruiz-Iruela, C, Padullés-Zamora, N, Podzamczer-Palter, D, et al. (2016). HLA-B*57:01 genotyping in the prevention of hypersensitivity to abacavir: 5 years of experience. Pharmacogenet Genomics 26(8): 390–396.Google Scholar
Saladores, P, Mürdter, T, Eccles, D, et al. (2015). Tamoxifen metabolism predicts drug concentrations and outcome in premenopausal patients with early breast cancer. Pharmacogenomics J 15(1): 84–94.Google Scholar
Sarfo, FS, Zhang, Y, Egan, D, et al. (2014). Pharmacogenetic associations with plasma efavirenz concentrations and clinical correlates in a retrospective cohort of Ghanaian HIV-infected patients. J Antimicrob Chemother 69(2): 491–499.Google Scholar
Schelleman, H, Chen, J, Chen, Z, et al. (2008). Dosing algorithms to predict warfarin maintenance dose in Caucasians and African Americans. Clin Pharmacol Ther 84: 332–339.Google Scholar
Schmidt, KT, Chau, CH, Price, DK, and Figg, WD (2016). Precision oncology medicine: the clinical relevance of patient-specific biomarkers used to optimize cancer treatment. J Clin Pharmacol 56(12): 1484–1499.Google Scholar
Shah, SS, Rockett, KA, Jallow, M, et al. (2016). Heterogeneous alleles comprising G6PD deficiency trait in West Africa exert contrasting effects on two major clinical presentations of severe malaria. Malar J 15: 13.Google Scholar
Shekalaghe, SA, Ter Braak, R, Daou, M, et al. (2010). In Tanzania, hemolysis after a single dose of primaquine coadministered with an artemisinin is not restricted to glucose-6-phosphate dehydrogenase-deficient (G6PD A-) individuals. Antimicrob Agents Chemother 54(5): 1762–1768.Google Scholar
Shi, C, Yan, W, Wang, G, et al. (2015). Pharmacogenetics-based versus conventional dosing of warfarin: a meta-analysis of randomized controlled trials. PLoS One 10(12): e0144511.Google Scholar
Shord, SS, Cavallari, LH, Gao, W, et al. (2009). The pharmacokinetics of codeine and its metabolites in Blacks with sickle cell disease. Eur J Clin Pharmacol 65: 651–658.Google Scholar
Small, CB, Margolis, DA, Shaefer, MS, and Ross, LL (2017). HLA-B*57:01 allele prevalence in HIV-infected North American subjects and the impact of allele testing on the incidence of abacavir-associated hypersensitivity reaction in HLA-B*57:01-negative subjects. BMC Infect Dis 17(1): 256.Google Scholar
Soko, ND, Masimirembwa, C, and Dandara, C (2016). Pharmacogenomics of rosuvastatin: a glocal (global+local) African perspective and expert review on a statin drug. OMICS 20(9): 498–509.Google Scholar
Sun, Q, Liu, HP, Zheng, RJ, et al. (2017). Genetic polymorphisms of SLCO1B1, CYP2E1 and UGT1A1 and susceptibility to anti-tuberculosis drug-induced hepatotoxicity: a Chinese population-based prospective case–control study. Clin Drug Investig 37(12): 1125–1136.Google Scholar
Sundelin, E, Gormsen, LC, Jensen, JB, et al. (2017). Genetic polymorphisms in organic cation transporter 1 attenuates hepatic metformin exposure in humans. Clin Pharmacol Ther 102(5): 841–848.Google Scholar
Swart, M, Ren, Y, Smith, P, and Dandara, C (2012a). ABCB1 4036A>G and 1236C>T polymorphisms affect plasma efavirenz levels in South African HIV/AIDS patients. Front Genet 3: 236.Google Scholar
Swart, M, Whitehorn, H, Ren, Y, et al. (2012b). PXR and CAR single nucleotide polymorphisms influence plasma efavirenz levels in South African HIV/AIDS patients. BMC Med Genet 13: 112.Google Scholar
Swart, M, Skelton, M, Ren, Y, et al. (2013). High predictive value of CYP2B6 SNPs for steady-state plasma efavirenz levels in South African HIV/AIDS patients. Pharmacogenet Genomics 23: 415–427.Google Scholar
Swen, JJ, Nijenhuis, M, De Boer, A, et al. (2011). Pharmacogenetics: from bench to byte – an update of guidelines. Clin Pharmacol Ther 89: 662–673.Google Scholar
Takeuchi, F, Mcginnis, R, Bourgeois, S, et al. (2009). A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. PLoS Genet 5(3): e1000433.Google Scholar
Tang, T, Liu, J, Zuo, K, et al. (2015). Genotype-guided dosing of coumarin anticoagulants: a meta-analysis of randomized controlled trials. J Cardiovasc Pharmacol Ther 20(4): 387–394.Google Scholar
Thein, SL and Menzel, S (2009). Discovering the genetics underlying foetal haemoglobin production in adults. Br J Haematol 145: 455–467.Google Scholar
Thomford, N, Dzobo, K, Chopera, D, et al. (2015). Pharmacogenomics implications of using herbal medicinal plants on African populations in health transition. Pharmaceuticals 8: 637.Google Scholar
Thorn, CF, Klein, TE, and Altman, RB (2013). PharmGKB: the Pharmacogenomics Knowledge Base. Methods Mol Biol 1015: 311–320.Google Scholar
Toure, MC, Niang, A, Diop, C, et al. (2016). Prevention of isoniazid toxicity by NAT2 genotyping in Senegalese tuberculosis patients. Toxicol Rep 3: 826–831.CrossRefGoogle ScholarPubMed
Twist, GP, Gaedigk, A, Miller, NA, et al. (2016). Constellation: a tool for rapid, automated phenotype assignment of a highly polymorphic pharmacogene, CYP2D6, from whole-genome sequences. NPJ Genom Med 1: 15007.Google Scholar
UNAIDS (2016). 2016–2021 Treatment Strategy. Available at: www.unaids.org/sites/default/files/media_asset/20151027_UNAIDS_PCB37_15_18_EN_rev1.pdf.Google Scholar
UNAIDS (2017). Data Book. Available at: www.unaids.org/en/resources/documents/2017/2017_data_book.Google Scholar
Vasiliou, V, Vasiliou, K, and Nebert, DW (2009). Human ATP-binding cassette (ABC) transporter family. Hum Genomics 3(3): 281–290.Google Scholar
Vo, TT and Varghese Gupta, S (2016). Role of Cytochrome P450 2B6 pharmacogenomics in determining efavirenz-mediated central nervous system toxicity, treatment outcomes, and dosage adjustments in patients with human immunodeficiency virus infection. Pharmacotherapy 36(12): 1245–1254.Google Scholar
Von Seidlein, L, Auburn, S, Espino, F, et al. (2013). Review of key knowledge gaps in glucose-6-phosphate dehydrogenase deficiency detection with regard to the safe clinical deployment of 8-aminoquinoline treatment regimens: a workshop report. Malar J 12: 112.Google Scholar
Wadelius, M (2014). Warfarin pharmacogenetics: it matters if you’re black or white. Blood 124(14): 2171.Google Scholar
Wang, P, Pradhan, K, Zhong, XB, and Ma, X (2016). Isoniazid metabolism and hepatotoxicity. Acta Pharm Sin B 6(5): 384–392.Google Scholar
Ward, BA, Gorski, JC, Jones, DR, et al. (2003). The cytochrome P450 2B6 (CYP2B6) is the main catalyst of efavirenz primary and secondary metabolism: implication for HIV/AIDS therapy and utility of efavirenz as a substrate marker of CYP2B6 catalytic activity. J Pharmacol Exp Ther 306(1): 287–300.Google Scholar
Ware, RE, Eggleston, B, Redding-Lallinger, R, et al. (2002). Predictors of fetal hemoglobin response in children with sickle cell anemia receiving hydroxyurea therapy. Blood 99: 10–14.Google Scholar
Ware, RE, Despotovic, JM, Mortier, NA, et al. (2011). Pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea treatment for children with sickle cell anemia. Blood 118: 4985–4991.Google Scholar
Watson, J, Taylor, WR, Menard, D, Kheng, S, and White, NJ (2017). Modelling primaquine-induced haemolysis in G6PD deficiency. Elife 6: e23061.Google Scholar
Weiner, M, Peloquin, C, Burman, W, et al. (2010). Effects of tuberculosis, race, and human gene SLCO1B1 polymorphisms on rifampin concentrations. Antimicrob Agents Chemother 54(10): 4192–4200.Google Scholar
Weinshilboum, RM and Wang, L (2017). Pharmacogenomics: precision medicine and drug response. Mayo Clin Proc 92(11): 1711–1722.Google Scholar
Wennerholm, A, Johansson, I, Hidestrand, M, et al. (2001). Characterization of the CYP2D6*29 allele commonly present in a black Tanzanian population causing reduced catalytic activity. Pharmacogenetics 11: 417–427.Google Scholar
Wennerholm, A, Dandara, C, Sayi, J, et al. (2002). The African-specific CYP2D617 allele encodes an enzyme with changed substrate specificity. Clin Pharmacol Ther 71: 77–88.Google Scholar
WHO (2016). Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach, 2nd edn. Available at: www.who.int/hiv/pub/arv/chapter4.pdf?ua=1 (accessed January 2, 2017).Google Scholar
Wonkam, A (2017). Is there a role for pharmacogenetics in the treatment of sickle cell disease? Pharmacogenomics 18(4): 321–325.Google Scholar
Wonkam, A, Ngo Bitoungui, VJ, Vorster, AA, et al. (2014). Association of variants at BCL11A and HBS1L-MYB with hemoglobin F and hospitalization rates among sickle cell patients in Cameroon. PLoS One 9: e92506.Google Scholar
Wright, GE, Niehaus, DJ, Drogemoller, BI, et al. (2010). Elucidation of CYP2D6 genetic diversity in a unique African population: implications for the future application of pharmacogenetics in the Xhosa population. Ann Hum Genet 74: 340–350.Google Scholar
Yang, JJ and Bhojwani, D (2013). Thiopurine S-methyltransferase pharmacogenetics in childhood acute lymphoblastic leukemia. Methods Mol Biol 999: 273–284.Google Scholar
Yang, JJ, Landier, W, Yang, W, et al. (2015). Inherited NUDT15 variant is a genetic determinant of mercaptopurine intolerance in children with acute lymphoblastic leukemia. J Clin Oncol 33(11): 1235–1242.Google Scholar
Yee, MM, Josephson, C, Hill, CE, et al. (2013). Cytochrome P450 2D6 polymorphisms and predicted opioid metabolism in African American children with sickle cell disease. J Pediatr Hematol Oncol 35: e301–e305.Google Scholar
Zanger, UM and Klein, K (2013). Pharmacogenetics of cytochrome P450 2B6 (CYP2B6): advances on polymorphisms, mechanisms, and clinical relevance. Front Genet 4: 24.Google Scholar
Zanger, UM and Schwab, M (2013). Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 138(1): 103–141.Google Scholar
Zembutsu, H (2015). Pharmacogenomics toward personalized tamoxifen therapy for breast cancer. Pharmacogenomics 16: 287–296.Google Scholar
Zhou, K, Donnelly, L, Burch, L, et al. (2010). Loss-of-function CYP2C9 variants improve therapeutic response to sulfonylureas in type 2 diabetes: a Go-DARTS study. Clin Pharmacol Ther 87(1): 52–56.Google Scholar

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