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Koyejo, Oluwatosin D. (2021) CHARACTERISATION OF MED-12 MUTATIONS IN UTERINE LEIOMYOMAS OF NIGERIAN WOMEN. Masters thesis, Covenant University Ota..

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Uterine fibroids (leiomyomas) are typical benign smooth muscle pelvic tumours in women of reproductive years. Its occurrence depends on race, age at menarche and has been found to arise in about 17.9%-26% of Nigerian women. MED-12, a transcriptional regulator, is known to harbour genetic mutations causal to the pathogenesis of leiomyomas in roughly 70% of women worldwide. However, the precise relationship between genetic mutations and protein/disease phenotype is not well-explained. The mutation frequency in Nigerian women is also unknown. The aim of this study was to characterize MED-12 mutations in leiomyomas of Nigerian women and apply the molecular docking methodology in understanding the binding of target-directed phytochemicals to this gene. The study was a multi-centre cross-sectional study conducted in Ogun and Abuja, Nigeria. DNA was extracted from the fibroid tissue collected, and MED-12 gene amplified followed by sequencing to identify the corresponding mutations. For Bioinformatics analysis phytochemicals were docked unto the active site of the MED-12 gene to quantify their binding affinities, thus identifying lead compounds from indigenous sources for the possible treatment and management of fibroid tumours. Among the included patients, 24% (6/24) of their leiomyomas had MED-12 missense, nonsense, frameshift, insertion and deletion mutations in a least one of their sequences. Amentoflavone, a biflavonoid, had the highest binding affinity of 10.2 to the MED-12 gene. This study is the first to characterise MED-12 mutations from Nigeria and agrees with previous findings that somatic MED-12 mutations are critical to the development and progression of uterine leiomyomas irrespective of ethnic background. Therefore, we recommend that mutation screening can assist in molecular diagnostics of uterine leiomyomas. Furthermore, in vivo studies and clinical trials should be promoted to aid the development of these high binding phytochemicals as treatment options.

Item Type: Thesis (Masters)
Subjects: Q Science > Q Science (General)
Q Science > QH Natural history
Divisions: Faculty of Engineering, Science and Mathematics > School of Chemistry
Faculty of Medicine, Health and Life Sciences > School of Biological Sciences
Depositing User: Mrs Patricia Nwokealisi
Date Deposited: 14 Mar 2022 12:16
Last Modified: 14 Mar 2022 12:16

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