Browsing by Author "Dias, Stephanie"

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    DNA methylation of FKBP5 in South African women : associations with obesity and insulin resistance
    (BMC, 2020-09) Willmer, Tarryn; Goedecke, Julia H.; Dias, Stephanie; Louw, Johan; Pheiffer, Carmen
    Background: Disruption of the hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system associated with the stress response, has been hypothesized to contribute to obesity development. This may be mediated through epigenetic modulation of HPA axis-regulatory genes in response to metabolic stressors. The aim of this study was to investigate adipose tissue depot-specific DNA methylation differences in the glucocorticoid receptor (GR) and its co-chaperone, FK506-binding protein 51 kDa (FKBP5), both key modulators of the HPA axis. Methods: Abdominal subcutaneous adipose tissue (ASAT) and gluteal subcutaneous adipose tissue (GSAT) biopsies were obtained from a sample of 27 obese and 27 normal weight urban-dwelling South African women. DNA methylation and gene expression were measured by pyrosequencing and quantitative real-time PCR, respectively. Spearman's correlation coefficients, orthogonal partial least-squares discriminant analysis and multivariable linear regression were performed to evaluate the associations between DNA methylation, messenger RNA (mRNA) expression and key indices of obesity and metabolic dysfunction. Results: Two CpG dinucleotides within intron 7 of FKBP5 were hypermethylated in both ASAT and GSAT in obese compared to normal weight women, while no differences in GR methylation were observed. Higher percentage methylation of the two FKBP5 CpG sites correlated with adiposity (body mass index and waist circumference), insulin resistance (homeostasis model for insulin resistance, fasting insulin and plasma adipokines) and systemic inflammation (c-reactive protein) in both adipose depots. GR and FKBP5 mRNA levels were lower in GSAT, but not ASAT, of obese compared to normal weight women. Moreover, FKBP5 mRNA levels were inversely correlated with DNA methylation and positively associated with adiposity, metabolic and inflammatory parameters. Conclusions: These findings associate dysregulated FKBP5 methylation and mRNA expression with obesity and insulin resistance in South African women. Additional studies are required to assess the longitudinal association of FKBP5 with obesity and associated co-morbidities in large population-based samples.
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    DNA methylation of FKBP5 in South African women : associations with obesity and insulin resistance
    (BMC (part of Springer Nature), 2020-09-21) Willmer, Tarryn; Goedecke, Julia H.; Dias, Stephanie; Louw, Johan; Pheiffer, Carmen
    Background: Disruption of the hypothalamic–pituitary–adrenal (HPA) axis, a neuroendocrine system associated with the stress response, has been hypothesized to contribute to obesity development. This may be mediated through epigenetic modulation of HPA axis-regulatory genes in response to metabolic stressors. The aim of this study was to investigate adipose tissue depot-specific DNA methylation differences in the glucocorticoid receptor (GR) and its co-chaperone, FK506-binding protein 51 kDa (FKBP5), both key modulators of the HPA axis. Methods: Abdominal subcutaneous adipose tissue (ASAT) and gluteal subcutaneous adipose tissue (GSAT) biopsies were obtained from a sample of 27 obese and 27 normal weight urban-dwelling South African women. DNA methylation and gene expression were measured by pyrosequencing and quantitative real-time PCR, respectively. Spearman’s correlation coefficients, orthogonal partial least-squares discriminant analysis and multivariable linear regression were performed to evaluate the associations between DNA methylation, messenger RNA (mRNA) expression and key indices of obesity and metabolic dysfunction. Results: Two CpG dinucleotides within intron 7 of FKBP5 were hypermethylated in both ASAT and GSAT in obese compared to normal weight women, while no differences in GR methylation were observed. Higher percentage methylation of the two FKBP5 CpG sites correlated with adiposity (body mass index and waist circumference), insulin resistance (homeostasis model for insulin resistance, fasting insulin and plasma adipokines) and systemic inflammation (c-reactive protein) in both adipose depots. GR and FKBP5 mRNA levels were lower in GSAT, but not ASAT, of obese compared to normal weight women. Moreover, FKBP5 mRNA levels were inversely correlated with DNA methylation and positively associated with adiposity, metabolic and inflammatory parameters. Conclusions: These findings associate dysregulated FKBP5 methylation and mRNA expression with obesity and insulin resistance in South African women. Additional studies are required to assess the longitudinal association of FKBP5 with obesity and associated co-morbidities in large population-based samples.
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    Intimate partner violence: a risk factor for gestational diabetes
    (MDPI, 2020-10) Pheiffer, Carmen; Dias, Stephanie; Adam, Sumaiya
    The early detection and management of gestational diabetes mellitus (GDM) is an important public health goal. GDM, which is defined as a glucose intolerance that develops during pregnancy, affects about 14% of pregnancies globally, and without effective treatment, it is associated with adverse short- and long-term maternal and neonatal outcomes. Risk-factor screening is an acceptable and affordable strategy to enable risk stratification and intervention. However, common biological risk factors such as overweight or obesity, excessive gestational weight gain, and family history of diabetes often have poor predictive ability, failing to identify a large proportion of women at risk of developing GDM. Accumulating evidence implicate psychosocial factors in contributing to GDM risk. As such, intimate partner violence (IPV), through its contributing effects on maternal stress and depression, presents a plausible risk factor for GDM. Experiencing IPV during pregnancy may dysregulate the hypothalamus-pituitary-adrenal (HPA) axis, leading to increased cortisol secretion and insulin resistance. These effects may exacerbate the insulin-resistant environment characteristic of pregnancy, thus increasing GDM risk. This review explores the relationship between IPV and GDM. We highlight studies that have linked IPV with GDM and propose a biological mechanism that connects IPV and GDM. Recommendations for IPV screening strategies to prevent GDM are discussed.
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    MicroRNA expression profiling in peripheral blood mononuclear cells and serum of type 2 diabetic, pre-diabetic and normo-glycaemic individuals
    (Stellenbosch : Stellenbosch University, 2016-03) Dias, Stephanie; Pheiffer, Carmen; Hemmings, Sian; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences. Molecular Biology and Human Genetics.
    ENGLISH ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs that play a fundamental role in cellular function by regulating messenger RNA gene expression. Alterations in miRNA expression are implicated in metabolic dysregulation, with several studies reporting the involvement of miRNAs in the pathophysiology of Type 2 diabetes (T2D). Recently, circulating miRNAs have attracted considerable interest as biomarkers to identify individuals at risk for T2D, thus we hypothesised that circulating miRNA could be used as markers for T2D progression. The aim of this study was to determine whether miRNA expression profiles differ between diabetic, pre-diabetic and normo-glycaemic individuals. Individuals were recruited from local communities and classified as diabetic, pre-diabetic or normo-glycaemic according to World Health Organization criteria, whereafter miRNAs were extracted from peripheral blood mononuclear cells (PBMCs) and serum of age-, gender-, ethnicity- and BMI-matched diabetic (n=4), pre-diabetic (n=4) and normo-glycaemic (n=4) individuals. MiRNAs extracted from PBMCs were sequenced using the Illumina HiSeq 2500 platform, and validated by quantitative real time PCR (qRT-PCR) in PBMCs and serum of these individuals. Moreover, bioinformatics was conducted using various target prediction programs (TargetScan, DIANA and PITA) and the DAVID functional gene annotation tool to assign biological significance to the differentially expressed miRNAs identified by sequencing. Sequencing showed that 267 (pre-diabetics vs. normo-glycaemics), 277 (diabetics vs. normo-glycaemics) and 267 (pre-diabetics vs. diabetics) miRNAs were differentially expressed between groups. Of these, five differentially expressed miRNAs (miR-27b, miR-379, miR-21, miR-98 and miR-143) were selected for validation by qRT-PCR in PBMCs. Only miR-143 and miR-27b were significantly differentially expressed using qRT-PCR, although the results for miR-143 were different compared to the sequencing data. MiR-143 was upregulated in pre-diabetics compared to normo-glycaemic individuals (1.40-fold, p≤0.01), whereas sequencing showed upregulation of miR-143 in diabetics compared to pre-diabetics (1.75-fold, p≤0.05). The differential expression of miR-27b was consistent between qRT-PCR (1.55-fold; p=0.07) and sequencing (1.15-fold; p<0.01), where both methods showed upregulation in pre-diabetics compared to normo-glycaemic individuals. The expression of miR-27b was similarly upregulated in serum of pre-diabetics compared to normo-glycaemic individuals (2.0-fold; p≤0.05). Furthermore, five novel miRNAs identified by sequencing were successfully validated in PBMCs of diabetic, pre-diabetic and normo-glycaemic individual. Sequencing and qRT-PCR showed that miR-27b was upregulated in PBMCs and serum of pre-diabetics compared to normo-glycaemic individuals. Bioinformatics identified peroxisome proliferator-activated receptor gamma (Pparg) as a target for miR-27b. PPARG is an insulin sensitizing agent, thus we speculate that increased miR-27b expression in pre-diabetes suppresses Pparg, thereby inhibiting insulin signaling and subsequently decreasing glucose uptake. The increased insulin and glucose levels observed in the pre-diabetic individuals support this idea, although further work is required to confirm this hypothesis. In conclusion, we showed that miRNA profiles differ during T2D progression, and are able to discriminate between diabetic, pre-diabetic and normo-glycaemic individuals. To our knowledge, this is the first study to report differential expression of miR-27b during T2D, suggesting its potential as a biomarker that could be incorporated into predictive models for the identification of high risk individuals. However, miRNA profiling in a larger sample
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    Spatial and temporal trends of SARS-CoV-2 RNA from wastewater treatment plants over 6 weeks in Cape Town, South Africa
    (MDPI, 2021-11-17) Street, Renee; Mathee, Angela; Mangwana, Noluxabiso; Dias, Stephanie; Sharma, Jyoti Rajan; Ramharack, Pritika; Louw, Johan; Reddy, Tarylee; Brocker, Ludwig; Surujlal-Naicker, Swastika; Berkowitz, Natacha; Malema, Mokaba Shirley; Nkambule, Sizwe; Webster, Candice; Mahlangeni, Nomfundo; Gelderblom, Huub; Mdhluli, Mongezi; Gray, Glenda; Muller, Christo; Johnson, Rabia
    Recent scientific trends have revealed that the collection and analysis of data on the occurrence and fate of SARS-CoV-2 in wastewater may serve as an early warning system for COVID-19. In South Africa, the first COVID-19 epicenter emerged in the Western Cape Province. The City of Cape Town, located in the Western Cape Province, has approximately 4 million inhabitants. This study reports on the monitoring of SARS-CoV-2 RNA in the wastewater of the City of Cape Town’s wastewater treatment plants (WWTPs) during the peak of the epidemic. During this period, the highest overall median viral RNA signal was observed in week 1 (9200 RNA copies/mL) and declined to 127 copies/mL in week 6. The overall decrease in the amount of detected viral SARS-CoV-2 RNA over the 6-week study period was associated with a declining number of newly identified COVID-19 cases in the city. The SARS-CoV-2 early warning system has now been established to detect future waves of COVID-19.