Department of Biochemistry

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    GENETIC POLYMORPHISMS IN ERCC6 AND CYP17A1 AND THEIR ASSOCIATION WITH VITAMIN-D LEVELS IN NIGERIAN PROSTATE CANCER PATIENTS
    (Covenant University Ota, 2025-04) AMADI, EMMANUEL CHIMUEBUKA; Covenant University Dissertation
    Prostate cancer (PCa) constitutes the principal cause of cancer-related deaths among males over 40 in Africa, especially in Nigeria. By 2030, 10.8% of males may develop PCa before 75. The aggressiveness of PCa in Blacks versus Caucasians is not well understood. Mutations in tumour-specific genes like Excision Repair Cross-Complementation Group 6 (ERCC6) and Cytochrome P450 Family 17 Subfamily A Member 1 (CYP17A1) may serve as diagnostic biomarkers. ERCC6, involved in DNA repair, and CYP17A1, key in androgen production, are linked to PCa progression. This study assessed ERCC6 rs2228528 and CYP17A1 rs4919686 polymorphisms and their relation to vitamin D (VD) and androgen receptor (AR) levels in Nigerian PCa patients. Vitamin D (VD) insufficiency is linked with increased prostate cancer (PCa) mortality and influences energy metabolism in normal prostate cells. The Androgen Receptor (AR) regulates vital genes in prostate cancer development and is more common in Black populations. Exploring ERCC6 and CYP17A1 in relation to VD and AR could improve PCa diagnosis. This study evaluated the association between ERCC6 rs2228528 (C > T) and CYP17A1 rs4919686 (A > C) polymorphisms, located in ERCC6 exon 11 and the CYP17A1 promoter, respectively, vis-à-vis VD and AR levels in Nigerian PCa patients. Genotyping employed real-time PCR with TaqMan assays, while enzyme-linked immunosorbent assay (ELISA) was used to measure VD and AR levels. The data was then analysed using Excel, SPSS, and R. Results revealed a higher presence of ERCC6 rs2228528 wildtype genotypes in cases (37%) compared to controls (30%) and a lower presence of CYP17A1 rs4919686 wildtype genotypes in cases (46%) versus controls (48%). No significant associations (p > 0.05) were found between these polymorphisms. Nevertheless, rs2228528 shows promise as a PCa biomarker. VD levels were higher in cases (52.49 ng/mL) than in control (47.93 ng/mL), while difference in androgen levels were not significant (p > 0.05). Lastly, ERCC6 polymorphism, but not CYP17A1, shows potential as a possible biomarker for PCa. Larger studies are needed for definitive conclusions.
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    GENETIC POLYMORPHISMS IN ERCC6 AND CYP17A1 AND THEIR ASSOCIATION WITH VITAMIN-D LEVELS IN NIGERIAN PROSTATE CANCER PATIENTS
    (Covenant University Ota, 2025-04) AMADI EMMANUEL CHIMUEBUKA; Covenant Uniersity Dissertation
    Prostate cancer (PCa) constitutes the principal cause of cancer-related deaths among males over 40 in Africa, especially in Nigeria. By 2030, 10.8% of males may develop PCa before 75. The aggressiveness of PCa in Blacks versus Caucasians is not well understood. Mutations in tumour-specific genes like Excision Repair Cross-Complementation Group 6 (ERCC6) and Cytochrome P450 Family 17 Subfamily A Member 1 (CYP17A1) may serve as diagnostic biomarkers. ERCC6, involved in DNA repair, and CYP17A1, key in androgen production, are linked to PCa progression. This study assessed ERCC6 rs2228528 and CYP17A1 rs4919686 polymorphisms and their relation to vitamin D (VD) and androgen receptor (AR) levels in Nigerian PCa patients. Vitamin D (VD) insufficiency is linked with increased prostate cancer (PCa) mortality and influences energy metabolism in normal prostate cells. The Androgen Receptor (AR) regulates vital genes in prostate cancer development and is more common in Black populations. Exploring ERCC6 and CYP17A1 in relation to VD and AR could improve PCa diagnosis. This study evaluated the association between ERCC6 rs2228528 (C > T) and CYP17A1 rs4919686 (A > C) polymorphisms, located in ERCC6 exon 11 and the CYP17A1 promoter, respectively, vis-à-vis VD and AR levels in Nigerian PCa patients. Genotyping employed real-time PCR with TaqMan assays, while enzyme-linked immunosorbent assay (ELISA) was used to measure VD and AR levels. The data was then analysed using Excel, SPSS, and R. Results revealed a higher presence of ERCC6 rs2228528 wildtype genotypes in cases (37%) compared to controls (30%) and a lower presence of CYP17A1 rs4919686 wildtype genotypes in cases (46%) versus controls (48%). No significant associations (p > 0.05) were found between these polymorphisms. Nevertheless, rs2228528 shows promise as a PCa biomarker. VD levels were higher in cases (52.49 ng/mL) than in control (47.93 ng/mL), while difference in androgen levels were not significant (p > 0.05). Lastly, ERCC6 polymorphism, but not CYP17A1, shows potential as a possible biomarker for PCa. Larger studies are needed for definitive conclusions. Keywords: Black Populations and Cancer, Gene
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    In-Silico, Nutritional and Anti-inflammatory Studies on Trametes versicolor (L.) Lloyd and Flammulina velutipes (Curtis) Singer
    (Covenant University Ota, 2025-03) IYEKEKPOLOR, OSAMUDIAME MOSES; Covenant University, Dissertation
    Mushrooms are recognized as functional foods due to their rich phytochemical diversity and nutritional and therapeutic value. This study investigated the health-promoting potential of two understudied species, Trametes versicolor and Flammulina velutipes, through an approach that integrated phytochemical analysis, nutritional profiling, anti-inflammatory investigation, and in-silico evaluation. Preliminary phytochemical screening was carried out using standard methods. Proximate and micronutrient analyses were carried out using AOAC methods. High-performance Liquid Chromatography (HPLC) was utilized for bioactive compound quantification. Anti-inflammatory activity was investigated via the albumin denaturation assay and compared with a standard anti-inflammatory drug (Prednisolone). Molecular docking was performed using the Swiss dock platform utilizing the AutoDock Vina algorithm. Preliminary phytochemical screening identified T.versicolor as rich in saponins, phenols, tannins, glycosides, and emodins, while F.velutipes contained high flavonoids, alkaloids, saponins, and phenols. Nutritional profiling revealed F.velutipes as a nutrient-dense species with higher energy (491.57 kcal/100g), protein (24.71%), and fiber (15.12%) compared to Trametes versicolor (426.73 kcal/100g, 19.66% protein, 12.42% fiber). Both mushrooms exhibited significant mineral content, including potassium, magnesium, and calcium, with F.velutipes containing elevated vitamin C (77.54 mg/100g) and T.versicolor higher vitamin B2 (2.46 mg/100g). Anti-inflammatory activity, revealed T. versicolor exhibited low potency (IC50 1.073 × 1010 μg/mL), whereas F. velutipes exhibited superior efficacy (IC50 2.858μg/mL), outperforming prednisolone (IC50 2.231 × 1014 μg/mL). Computational molecular docking against HER2, a breast cancer target, revealed T.versicolor’s bioactive compounds—rutin, apigenin, and kaempferol—with binding affinities of -5.88, -5.81, and -5.78 kcal/mol, respectively, comparable to the standard drug doxorubicin (-5.43 kcal/mol). Similarly, F.velutipes’ orientin and catechin showed binding affinities of -5.24 and -5.70 kcal/mol, highlighting their anticancer potential. These findings underscore both species as nutrient-rich functional foods with robust anti-inflammatory activity and promising therapeutic relevance against breast cancer.
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    Frequency Of BRCA1 Polymorphisms (rs799917 and rs1799966) Among Nigerian Breast Cancer Patients
    (Covenant University Ota, 2025-03) OGUNNIYI, OLUWABUSAYO BUNMI; Covenant University, Dissertation
    Breast cancer (BCa) is the most diagnosed malignancy among women worldwide, with an estimated 2.3 million new cases and 666,103 deaths recorded in 2022. In Nigeria, BCa remains the leading cause of cancer-related mortality among women, accounting for 32,278 (25.3%) new cases and 16,322 (20.5%) deaths in 2022. Breast cancer gene 1 (BRCA1) is a tumour suppressor gene involved in DNA damage repair, cell cycle regulation, and maintenance of genome stability. Studies suggest that genetic factors, such as Single Nucleotide Polymorphism (SNPs) in the BRCA1 genes, play a pivotal role in the development of cancers. The BRCA1 gene harbors specific SNPs within its coding sequence, including rs799917 and rs1799966. These SNPs interfere with the interaction between BRCA1 mRNA and miR-638, significantly decreasing BRCA1 expression among individuals carrying these variants. Several studies have reported correlations between BRCA1 polymorphisms rs799917 and rs1799966 with the risk of BCa. However, this relationship remains controversial. This study assesses the frequency of BRCA1 rs799917 and rs1799966 polymorphisms and their association with BCa in Nigeria. The case-control study included 500 BCa patients and 200 paired healthy controls. TaqMan genotyping assay was used to determine the genotypes of rs799917 and rs1799966 polymorphisms. Using logistic regression and Pearson's chi-square test, a statistically significant difference (p < 0.05) was identified in the genotype frequencies. The G allele of rs799917(p= 0.017; OR: 1.39) showed significant associations with the risk of breast cancer in Nigeria and, while globally reported as the wild-type allele, is observed as the variant allele in our population. The C Allele of rs1799966 confers a protective risk against breast cancer. Further study should focus on functional genomics to evaluate the interaction between miR-638 and the mRNA in individuals carrying this SNP, particularly in the Nigerian population. Keywords: breast
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    Programme: Molecular Biology
  • Collection
    Programme: BIochemistry