Srinivas Reddy Pallerla1, Darrel Ornelle Elion Assiana2, Le Thi Kieu Linh1, Frederick Nchang Cho3, Christian G Meyer4, Kaossarath Adédjokè Fagbemi5, Ayola Akim Adegnika6, Véronique Penlap Beng7, Eric A Achidi8, Gauthier Mesia Kahunu9, Mathew Bates10, Martin P Grobusch11, Peter G Kremsner6, Francine Ntoumi12, Thirumalaisamy P Velavan13. 1. Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany; Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Viet Nam. 2. Fondation Congolaise pour la Recherche Médicale (FCRM), Brazzaville, Congo; Faculty of Sciences and Technology, University Marien Ngouabi, Brazzaville, Congo. 3. Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany; Department of Biochemistry and Molecular Biology, Faculty of Science, Laboratory of Infectious Diseases, Faculty of Health Sciences, University of Buea, Buea, Cameroon. 4. Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany; Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Viet Nam; Faculty of Medicine, Duy Tan University, Da Nang, Viet Nam. 5. Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany; Department of Biomedical Sciences, Laboratory of Cytogenetics and Medical Genetics, Faculty of Health Sciences, University of Abomey-Calavi, Benin. 6. Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany; Centre de Recherches Medicales de Lambarene, Lambarene, Gabon. 7. Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon. 8. Department of Biochemistry and Molecular Biology, Faculty of Science, Laboratory of Infectious Diseases, Faculty of Health Sciences, University of Buea, Buea, Cameroon. 9. Unit of Clinical Pharmacology and Pharmacovigilance, University of Kinshasa, Kinshasa, Democratic Republic of the Congo. 10. School of Life Sciences, University of Lincoln, Lincoln, United Kingdom. 11. Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany; Centre de Recherches Medicales de Lambarene, Lambarene, Gabon; Center for Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Amsterdam University Medical Centers, University of Amsterdam, The Netherlands. 12. Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany; Fondation Congolaise pour la Recherche Médicale (FCRM), Brazzaville, Congo; Faculty of Sciences and Technology, University Marien Ngouabi, Brazzaville, Congo. 13. Institute of Tropical Medicine, University of Tübingen, Wilhelmstrasse 27, 72074 Tübingen, Germany; Vietnamese-German Center for Medical Research, VG-CARE, Hanoi, Viet Nam; Fondation Congolaise pour la Recherche Médicale (FCRM), Brazzaville, Congo; Faculty of Medicine, Duy Tan University, Da Nang, Viet Nam. Electronic address: velavan@medizin.uni-tuebingen.de.
Abstract
BACKGROUND: HIV-infection, tuberculosis and malaria are the big three communicable diseases that plague sub-Saharan Africa. If these diseases occur as co-morbidities they require polypharmacy, which may lead to severe drug-drug-gene interactions and variation in adverse drug reactions, but also in treatment outcomes. Polymorphisms in genes encoding drug-metabolizing enzymes are the major cause of these variations, but such polymorphisms may support the prediction of drug efficacy and toxicity. There is little information on allele frequencies of pharmacogenetic variants of enzymes involved in the metabolism of drugs used to treat HIV-infection, TB and malaria in the Republic of Congo (ROC). The aim of this study was therefore to investigate the occurrence and allele frequencies of 32 pharmacogenetic variants localized in absorption distribution, metabolism and excretion (ADME) and non-ADME genes and to compare the frequencies with population data of Africans and non-Africans derived from the 1000 Genomes Project. RESULTS: We found significant differences in the allele frequencies of many of the variants when comparing the findings from ROC with those of non-African populations. On the other hand, only a few variants showed significant differences in their allele frequencies when comparing ROC with other African populations. In addition, considerable differences in the allele frequencies of the pharmacogenetic variants among the African populations were observed. CONCLUSIONS: The findings contribute to the understanding of pharmacogenetic variants involved in the metabolism of drugs used to treat HIV-infection, TB and malaria in ROC and their diversity in different populations. Such knowledge helps to predict drug efficacy, toxicity and ADRs and to inform individual and population-based decisions.
BACKGROUND:HIV-infection, tuberculosis and malaria are the big three communicable diseases that plague sub-Saharan Africa. If these diseases occur as co-morbidities they require polypharmacy, which may lead to severe drug-drug-gene interactions and variation in adverse drug reactions, but also in treatment outcomes. Polymorphisms in genes encoding drug-metabolizing enzymes are the major cause of these variations, but such polymorphisms may support the prediction of drug efficacy and toxicity. There is little information on allele frequencies of pharmacogenetic variants of enzymes involved in the metabolism of drugs used to treat HIV-infection, TB and malaria in the Republic of Congo (ROC). The aim of this study was therefore to investigate the occurrence and allele frequencies of 32 pharmacogenetic variants localized in absorption distribution, metabolism and excretion (ADME) and non-ADME genes and to compare the frequencies with population data of Africans and non-Africans derived from the 1000 Genomes Project. RESULTS: We found significant differences in the allele frequencies of many of the variants when comparing the findings from ROC with those of non-African populations. On the other hand, only a few variants showed significant differences in their allele frequencies when comparing ROC with other African populations. In addition, considerable differences in the allele frequencies of the pharmacogenetic variants among the African populations were observed. CONCLUSIONS: The findings contribute to the understanding of pharmacogenetic variants involved in the metabolism of drugs used to treat HIV-infection, TB and malaria in ROC and their diversity in different populations. Such knowledge helps to predict drug efficacy, toxicity and ADRs and to inform individual and population-based decisions.