Browsing by Subject "Pharmacogenomics"

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    Open Access
    Success stories in genomic medicine from resource-limited countries
    (Biomed Central Ltd, 2015) Mitropoulos, Konstantinos; Al Jaibeji, Hayat; Forero, Diego; Laissue, Paul; Wonkam, Ambroise; Lopez-Correa, Catalina; Mohamed, Zahurin; Chantratita, Wasun; Lee, Ming; Llerena, Adrian; Brand, Angela; Ali, Bassam; Patrinos, George
    In recent years, the translation of genomic discoveries into mainstream medical practice and public health has gained momentum, facilitated by the advent of new technologies. However, there are often major discrepancies in the pace of implementation of genomic medicine between developed and developing/resource-limited countries. The main reason does not only lie in the limitation of resources but also in the slow pace of adoption of the new findings and the poor understanding of the potential that this new discipline offers to rationalize medical diagnosis and treatment. Here, we present and critically discuss examples from the successful implementation of genomic medicine in resource-limited countries, focusing on pharmacogenomics, genome informatics, and public health genomics, emphasizing in the latter case genomic education, stakeholder analysis, and economics in pharmacogenomics. These examples can be considered as model cases and be readily replicated for the wide implementation of pharmacogenomics and genomic medicine in other resource-limited environments.
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    Open Access
    The role of warfarin pharmacogenomics on the time it takes to reach stable therapeutic International Normalized Ratio (INR) and on warfarin dose required to maintain stable therapeutic INR in Black African and Mixed Ancestry South Africans: a focus on CYP2C9 and VKORC1
    (2019) Makambwa, Edson; Ntsekhe, Mpiko; Dandara, Collet
    Warfarin, the most commonly prescribed anticoagulant, is principally metabolized by cytochrome P450 2C9 which functions by inhibiting the Vitamin K epoxide reductase. Genes CYP2C9 and VKORC1 code for these two proteins, respectively. CYP2C9 and VKORC1 exhibit genetic polymorphisms that have been shown to affect warfarin response and favorably facilitate warfarin dosing and improve clinical outcomes. However, none of these studies have involved populations from sub-Saharan Africa where the potential benefit of optimal dosing and reduced complications is greatest. Therefore, the thesis describes a study designed to investigate the role of genetic variations in CYP2C9 and VKORC1 on the time taken to reach a stable therapeutic international normalized ratio (INR) and warfarin dose required to maintain a therapeutic INR. This was a cross-sectional study of patients on warfarin to determine the relationship between genetic polymorphism in CYP2C9 and VKORC1 amongst black and mixed ancestry South Africans and clinical surrogates of warfarin metabolism. Medical records were accessed to determine time to INR and warfarin doses. DNA was extracted from blood samples, and genotyping for polymorphism in CYP2C9 (*2,*3,*8,*11) and VKORC1 (1173C>T, 1639G>A, 3730G>A) was accomplished by PCR-RFLP, Sanger sequencing and iPlex Mass Sequencing. Our results show that the genetic profile of CYP2C9 and VKORC1 differs between Black Africans (BA) and their Mixed Ancestry (MA) counterparts. VKORC1-1639AA genotype was observed at frequencies of 0.11 and 0.01 in the MA and BA, respectively. Time to stable INR was not influenced by CYP2C9 and VKORC1. Furthermore, compared to known genetic polymorphisms in these genes from population out of Africa, both qualitative and quantitative differences were observed. Finally, we found that VKORC1 genetic variation significantly affected the doses of warfarin in MA but had no effect in BA. These results suggest that further research in this area is warranted, and that it will be important to include populations from sub-Saharan Africa in future if the potential to develop personalized algorithms which integrate pharmacogenomics to assist with effective warfarin dosing and prevention of warfarin related complications is to be realized.