Browsing by Author "Blom, Dirk Jacobus"

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    9β Polymorphism of the Glucocorticoid Receptor Gene Appears to Have Limited Impact in Patients with Addison’s Disease
    (Public Library of Science, 2014) Ross, Ian Louis; Dandara, Collet; Swart, Marelize; Lacerda, Miguel; Schatz, Desmond; Blom, Dirk Jacobus
    BACKGROUND: Addison’s disease (AD) has been associated with an increased risk of cardiovascular disease. Glucocorticoid receptor polymorphisms that alter glucocorticoid sensitivity may influence metabolic and cardiovascular risk factors in patients with AD. The 9β polymorphism of the glucocorticoid receptor gene is associated with relative glucocorticoid resistance and has been reported to increase the risk of myocardial infarction in the elderly. We explored the impact of this polymorphism in patients with AD. Materials and METHODS: 147 patients with AD and 147 age, gender and ethnicity matched healthy controls were recruited. Blood was taken in a non-fasted state for plasma lipid determination, measurement of cardiovascular risk factors and DNA extraction. RESULTS: Genotype data for the 9β polymorphism was available for 139 patients and 146 controls. AD patients had a more atherogenic lipid profile characterized by an increase in the prevalence of small dense LDL (p = 0.003), increased triglycerides (p = 0.002), reduced HDLC (p<0.001) an elevated highly sensitive C-reactive protein (p = 0.01), compared with controls. The 9β polymorphism (at least one G allele) was found in 28% of patients and controls respectively. After adjusting for age, gender, ethnicity, BMI and hydrocortisone dose per metre square of body surface area in patients, there were no significant metabolic associations with this polymorphism and hydrocortisone doses were not higher in patients with the polymorphism. CONCLUSIONS: This study did not identify any associations between the 9β polymorphism and cardiovascular risk factors or hydrocortisone dose and determination of this polymorphism is therefore unlikely to be of clinical benefit in the management of patients with AD.
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    Dysbetalipoproteinaemia : clinical and laboratory aspects, changes in lipoprotein composition and remnant metabolism associated with lipid lowering drugs
    (2007) Blom, Dirk Jacobus; Marais, A David
    This thesis examines and reviews multiple aspects of dysbetalipoproteinaemia. Dysbetalipoproteinaemia is a severe, highly atherogenic mixed hyperlipidaernia characterized by the accumulation of remnants of triglyceride-rich lipoproteins. Genetic susceptibility is conferred by mutations in apolipoproteinE, but manifest hyperlipidaemia often only occurs in the presence of metabolic abnormalities that influence lipoprotein production or clearance. Normal lipid metabolism is briefly reviewed to enable a better understanding of the pathophysiology of dysbetalipoproteinaernia. Hepatic remnant clearance is reviewed in detail with particular emphasis on the roles of all hepatic lipoprotein receptors. The importance of differential hepatic lipoprotein receptor binding affinities according to apoE mutation is emphasized.
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    Polyacrylamide gradient gel electrophoresis for the diagnosis of dysbetalipoproteinaemia (Type III hyperlipidaemia)
    (2001) Blom, Dirk Jacobus; Marais, David
    Accurate phenotypic diagnosis of this disorder has generally relied on the quantitative analysis of centrifugally isolated VLDL. Analysis of VLDL chemical composition is not widely available due to the expense of acquiring ultracentrifuges and the highly-skilled staff necessary to perform the analyses. Genotypic diagnosis is somewhat more widely available, especially testing for the E2/E2 genotype which is the commonest underlying genotype in dysbetalipoproteinaemia. Testing for the rarer autosomal mutations of ApoE is restricted to a small number of centres only. In this study I will review dysbetalipoproteinaemia briefly and then describe and evaluate GGE as a new diagnostic technique for this disorder.
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    The prevalence of dysbetalipoproteinaemia in Ghanaian adults living in Accra
    (2024) Ateko, Richmond Owusu; Blackhurst, Dee Mary; Marais, David Adrian; Blom, Dirk Jacobus
    Background Dysbetalipoproteinaemia (dysβ) is a disorder characterised by elevated triglyceride-rich lipoprotein remnants leading to increased plasma levels of total cholesterol and triglyceride. Dysbetalipoproteinaemia is positively associated with premature cardiovascular disease. In several places worldwide, especially in sub-Saharan Africa, clinicians often miss the diagnosis of dysβ due to a lack of awareness of the disorder and its manifestations. Although the apo E2/2 isoform is the most common genetic cause of dysβ, other mutations in apo E, which are autosomal dominant, can also cause dysβ. The apo E arginine 145 cysteine (R145C) is such a mutation and is highly prevalent in the indigenous African population of South Africa. Its prevalence in Ghana is unknown. Aim The main aim of this study was to determine the prevalence of dysβ by a diagnostic electrophoresis technique in Ghanaians living in Accra, and to establish the genetic associations. Method(s) The study recruited 1032 participants, comprising 702 healthy controls, 268 diabetic patients, and 62 ischaemic heart disease (IHD) patients. Adult men and postmenopausal women were studied as dysβ is most commonly identified in these demographic groups. Anthropometric measurements and blood pressure readings were taken and recorded after participants consented. Blood samples were collected to analyse concentrations of creatinine, glucose, and triglyceride, total cholesterol, HDL-c, and calculated LDL-c. DNA analyses were conducted to identify the presence of the apoE genotype and the frequency of apoE (R145C) in the study population. Non-denaturing polyacrylamide gradient gel electrophoresis (PGGE) was used to screen for the dysβ phenotype by determining whether remnant-sized lipoproteins had accumulated in the characteristic pattern of dysβ Findings The study revealed the presence of dysβ within a subset of the Ghanaian population, with a notable association observed among individuals exhibiting apo ԑ2/2 homozygosity. Moreover, the study shed light on the utility of PGGE as an economical and practical screening tool for identifying dysβ cases. Additionally, investigating the clinical implications associated with dysβ in the Ghanaian population could provide valuable insights for healthcare providers and policymakers