Browsing by Author "Abrahams-October, Zainonesa"

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    The determination of the effect(s) of solute carrier family 22‑member 2 (SLC22A2) haplotype variants on drug binding via molecular dynamic simulation systems
    (Nature Research, 2022) Abrahams-October, Zainonesa; Johnson, Rabia; Cloete, Ruben
    Single nucleotide polymorphisms detected in the solute carrier member family-22 has been shown to result in a variable response in the treatment of type 2 diabetes mellitus with Metformin. This study predicted a three-dimensional protein structure for the SLC22A2 protein sequence using AlphaFold 2 and modelled five haplotypes within SLC22A2 protein structure observed in the Xhosa population of South Africa. The protein models were used to determine the effect(s) of haplotype variations on the transport function of Metformin and 10 other drugs by the SLC22A2 protein. Molecular dynamic simulation studies, molecular docking and interaction analysis of the five SLC22A2 haplotypes were performed in complex with the ligand 5RE in a POPC lipid bilayer to understand the mechanism of drug binding.
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    Effects of xhosa specific solute carrier family 22-member 2 haplotypes on the cellular uptake of metformin and cimetidine
    (Elsevier B.V., 2025) Abrahams-October, Zainonesa; Kippie, Yunus; Pearce, Keenau; Benjeddou, Mongi
    Background: Studies have shown that solute carrier transporters play an important role in the transport and distribution of metformin, and that genetic variation(s) in solute carrier genes have play a role in the variation of metformin efficacy and disposition observed in populations. This study aimed to determine the cellular uptake efficiency of metformin in SLC22A2 coding haplotypes of an indigenous South African population. Methods and results: To determine metformin and cimetidine cellular uptake in transfected HEK-293 cells, ultra high-performance liquid chromatography was used to quantitate substrate concentration(s). Haplotypes 3 and 4 showed decreased metformin uptake, and haplotypes 2 and 5 displayed increased metformin uptake in comparison to haplotype 1 (i.e. wildtype haplotype). Haplotypes 2–5 showed decreased uptake of cimetidine in comparison to haplotype 1, implying a reduced sensitivity to the inhibition of cimetidine. In all haplotypes, no significant transport was observed for metformin and cimetidine. Passive permeability of metformin was favoured in haplotypes 3 and 5, whilst the remaining haplotypes demonstrate higher passive permeability ratios in favour of cimetidine. Conclusion: Haplotype 4, which is characterised by the non-synonymous single nucleotide polymorphisms rs316019 and rs8177517, demonstrates potential impaired metformin transport.
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    Socio-demographic and modifiable risk factors of diabetes and hypertension among resource constrained patients from rural areas in mdantsane township in South Africa
    (Makerere University, 2020) Xhakaza, Lettilia; Abrahams-October, Zainonesa; Mohammednur, Mohammedmekin Mohammedseid
    Recently, developing countries have shown a dramatic increase in non-communicable diseases (NCDs). The burden of NCDs in South Africa has increased over the past years resulting in an estimated 37% of all-cause mortality and 16% of disability-adjusted life years. Currently, diabetes mellitus (DM) and hypertension (HTN) are the two most prevalent NCDs associated with the rapid increase in mortality. Objective: To demonstrate the socio-demographic and modifiable risk factors of diabetes mellitus (DM) and hypertension (HTN) among South African adults. Methods: A cross-sectional analytical study was conducted in the Cecilia Makiwane Hospital serving the residents of Mdantsane. Relevant socio-demographic data, anthropometric measurements, triplicate blood pressure, fasting blood glu-cose and lipogram analysis were obtained from 265 outpatients. Results: Multivariate anlysis shows that; salt intake, smoking, elevated triglycerides and decreased high-density lipoprotein levels were significantly associated with DM with adjusted odds ratio of 0.18 (p=0.002), 0.26 (p=0.048), 2.19 (p=0.006) and 0.38 (p=0.001), respectively.