http://hdl.handle.net/11189/5748 Sun, 16 Aug 2026 06:12:50 GMT 2026-08-16T06:12:50Z https://digitalknowledge.cput.ac.za:443/retrieve/26254/ http://hdl.handle.net/11189/5748 http://hdl.handle.net/11189/5641 Title: Genome-wide dna methylation in mixed ancestry individuals with diabetes and prediabetes from south africa Authors: Matsha, Tandi Edith; Pheiffer, Carmen; Humphries, Stephen E; Gamieldien, Junaid; Erasmus, Rajiv; Kengne, Andre Pascal Abstract: Aims. To conduct a genome-wide DNA methylation in individuals with type 2 diabetes, individuals with prediabetes, and control mixed ancestry individuals from South Africa. Methods. We used peripheral blood to perform genome-wide DNA methylation analysis in 3 individuals with screen detected diabetes, 3 individuals with prediabetes, and 3 individuals with normoglycaemia from the Bellville South Community, Cape Town, South Africa, who were age-, gender-, body mass index-, and duration of residency-matched. Methylated DNA immunoprecipitation (MeDIP) was performed by Arraystar Inc. (Rockville, MD, USA). Results. Hypermethylated DMRs were 1160 (81.97%) and 124 (43.20%), respectively, in individuals with diabetes and prediabetes when both were compared to subjects with normoglycaemia. Our data shows that genes related to the immune system, signal transduction, glucose transport, and pancreas development have altered DNA methylation in subjects with prediabetes and diabetes. Pathway analysis based on the functional analysis mapping of genes to KEGG pathways suggested that the linoleic acid metabolism and arachidonic acid metabolism pathways are hypomethylated in prediabetes and diabetes. Conclusions. Our study suggests that epigenetic changes are likely to be an early process that occurs before the onset of overt diabetes. Detailed analysis of DMRs that shows gradual methylation differences from control versus prediabetes to prediabetes versus diabetes in a larger sample size is required to confirm these findings. Fri, 01 Jan 2016 00:00:00 GMT http://hdl.handle.net/11189/5641 2016-01-01T00:00:00Z http://hdl.handle.net/11189/4927 Title: Association of the ENPP1 rs997509 polymorphism with obesity in South African mixed ancestry learners Authors: Matsha, Tandi Edith; Fanampe, Biotumelo L; Yako, Yandiswa Y; Hassan, Mogamat Shafick; Hoffmann, M; Van der Merwe, L; Erasmus, Rajiv Abstract: Background: The Ectonucleotide Pyrophosphatase Phosphodiesterase1 (ENPP1) polymorphisms have been associated with metabolic traits. There is no data on the effect of ENPP1 in South African children or adults. Objective: To investigate the role of K121Q (rs1044498), rs997509 and rs9402349 in obesity and other components of the metabolic syndrome. Design: A case-control study. Subjects: Sixty four obese and 64 lean mixed ancestry learners. Setting: Western Cape, South Africa. Main outcome measure: The ENPP1 rs997509T allele is independently associated with obesity in children of mixed ancestry from South Africa. Results: The T allele frequency of the rs997509 differed significantly between obese and controls, p=0.0100 and increased the risk of being obese, p = 0.0238. Furthermore, the estimated effect of the T allele was an increase of 8.6 cm in waist circumference, 10.2 kg in weight and a corresponding 4.9 kg/m2 in BMI. Individuals carrying both the 121Q and the T allele of rs997509 were more associated with obesity (odds ratio = 3.85, 95% CI: 1.13 to 13.09) whilst those carrying the C allele of rs997509 in the presence of 121Q were likely to be lean with odds ratio of obesity 0.41 (95% CI: 0.19 to 0.87). Conclusion: Our findings suggest that ENPP1 polymorphisms may contribute to different metabolic characteristics, all of which are associated with insulin resistance in mixed ancestry children of South Africa. However, a larger study is required to confirm findings of this study. Fri, 01 Jan 2010 00:00:00 GMT http://hdl.handle.net/11189/4927 2010-01-01T00:00:00Z http://hdl.handle.net/11189/4771 Title: HbA1c of 6.5% to diagnose diabetes mellitus – Does it work for us? – The Bellville South Africa study Authors: Zemlin, Annalise E; Matsha, Tandi Edith; Hassan, Mogamat Shafick; Erasmus, Rajiv Abstract: Diabetes is a disease fuelled by the increasing worldwide obesity epidemic with significant morbidity and mortality, and the World Health Organization (WHO) estimates that it will affect 366 million individuals worldwide by 2030 [1]. Its diagnosis was previously made either according to the WHO criteria which were updated in 2006 [2] using a fasting blood glucose sample and subsequent 75 g oral glucose tolerance test (OGTT) with blood taken for glucose determination again 2 hours after an oral glucose challenge, or according to the American Diabetes Association (ADA) criteria which were updated in 2005 [3], using only a fasting blood glucose level. Using ADA criteria only has been found to underestimate the prevalence of diabetes and misses those individuals with impaired glucose tolerance (IGT), a pre-diabetic state [4]. The disadvantage of both these diagnostic approaches is that they require the patient to fast and if need confirming, would require a second fasting sample. Glucose also has a large biological and diurnal variation and depends on recent carbohydrate intake and the OGTT is fairly invasive [5]. In 2010, the ADA updated their diagnostic criteria to include an OGTT as well [6]. On the other hand, HbA1c, which is formed by the attachment of glucose to various amino groups of haemoglobin and has been used since 1977 for the long-term (2–3 month) glycaemic control follow up of diabetes, has recently been advocated by the ADA as a diagnostic tool. In 2009, the International Expert Committee of the ADA issued a statement proposing an HbA1c value of 6.5% (48 mmol/mol) as a diagnostic level for the diagnosis of diabetes. This value was chosen, as it was found to be the value after which the incidence of retinopathy, a common complication that often is present before the actual diagnosis of diabetes is made, is increased [7]. This test would be advantageous, as it does not require a fasting sample and has much less intraindividual variation. Sat, 01 Jan 2011 00:00:00 GMT http://hdl.handle.net/11189/4771 2011-01-01T00:00:00Z http://hdl.handle.net/11189/4770 Title: Negative association of MC3R variants with weight and blood pressure in Cape Town pupils aged 11–16 years Authors: Yako, Yandiswa Y; Fanampe, Biotumelo L; Hassan, Mogamat Shafick; Erasmus, Rajiv; Van der Merwe, Lize; Matsha, Tandi Edith Abstract: Background. Human and animal studies support the role of MC4R and MC3R in human obesity, but limited data are available on the genetic contribution to obesity in South African populations. Objective. To screen obese-overweight South African pupils for MC3R and MC4R polymorphisms that may play a role in the development of obesity. Design. A cross-sectional study screened 227 obese-overweight (115 black and 112 coloured) and 204 normal weight (94 black, 110 coloured) school pupils for the presence of MC4R and MC3R polymorphisms using a single strand conformation polymorphism, subsequent sequencing, and allele specific restriction enzyme analysis. Results. Two polymorphisms were detected in the MC3R (T6K and V81I) but none in MC4R. After adjusting for age, gender and case-control status, the frequency distributions of T6K and V81I genotype and allele varied significantly between the ethnic groups. The frequency of the V81I A allele was significantly lower in coloured overweight-obesity than normal pupils. In coloured pupils, both polymorphisms were associated with obesity indices and total cholesterol. The T6K A allele was also associated with lower blood pressure. Likewise, different T6K-V81I haplotypes demonstrated negative associations with obesity indices and blood pressure. Conclusion. We demonstrated that the MC3R polymorphisms have a protective effect on metabolic traits; however, further analysis is required to confirm whether this translates to a lower incidence of metabolic syndrome in coloured populations. Sat, 01 Jan 2011 00:00:00 GMT http://hdl.handle.net/11189/4770 2011-01-01T00:00:00Z