Browsing by Author "De Buys, Keren"

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    Identifying relevant novel markers of cardiometabolic risk in the Cardiovascular Risk in Black South Africans (CRIBSA) Study
    (Stellenbosch : Stellenbosch University, 2019-04) De Buys, Keren; Hemmings, Sian M. J.; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Biomedical Sciences: Molecular Biology and Human Genetics.
    ENGLISH ABSTRACT: Non-communicable diseases are the second leading cause of death in South Africa. In South African Black individuals, risk factors for cardiovascular disease, such as hypertension, obesity and type 2 diabetes mellitus, are common. These individual risk factors for cardiovascular disease (dyslipidaemia, hypertension, obesity and type 2 diabetes) are the focus of the present study in the Black isiXhosa-speaking population of Cape Town. Previous studies, in European and North American populations, have identified single nucleotide polymorphisms (SNPs) in various genes to be associated with non-communicable diseases that are risk factors for cardiovascular disease. However, few studies have been conducted in sub-Saharan Africa and even fewer have been conducted in South Africa. Identifying genes that contribute to the development of cardiovascular disease may help to understand its pathophysiology, identify individuals at higher risk and novel targets may aid preventative and treatment strategies. The aim of this study was to determine if selected genetic markers in genes encoding the angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AT1R), transcription factor 7-like 2 (TCF7L2), fat-mass and obesity associated (FTO), melanocortin 4 receptor (MC4R) and tumour necrosis factor-alpha (TNFα) are associated with cardiovascular disease risk in South African Black individuals. Of the 1 116 samples available for this study, DNA was extracted from 936 samples. SNPs in each of these genes were selected based on previous findings of association with disease in other African populations. Genotypes were analysed under additive, dominant and recessive association models using the R Statistical Package, snpassoc. The I/I genotype of rs4646994 of ACE was associated with blood pressure (p=0.014) and LDL-C (p=0.038) under a recessive inheritance model, while the D/D genotypes was associated with obesity and waist circumference under additive (p=0.047 and p=0.044, respectively) and dominant (p=0.04351 and p=0.04437, respectively) inheritance models. rs17782313 of MC4R was nominally associated with type 2 diabetes mellitus under dominant (T/C and C/C genotypes) (p=0.054) and recessive (T/T genotype) (p=0.075) inheritance models; and rs229616 (A/A genotype) was nominally associated with HDL-C (p=0.059) and rs1297034 was nominally associated with type 2 diabetes mellitus (p=0.075) under recessive inheritance models. Suggestive evidence of association with disease was observed for many of the genes, but further studies are needed to confirm this. Genetic associations with obesity and type 2 diabetes mellitus, risk factors for cardiovascular disease, observed in other African, as well as European and American populations, were replicated in this study. Novel associations with disease in South Africa and sub-Saharan Africa are reported and cross-phenotype associations were observed. This study suggests that these genes are potentially causal in disease predisposition and progression in the South African Black population, where the prevalence of these diseases is high. This study suggests that this is an important population to study and further studies are warranted.