Introduction: The continual increase of type 2 diabetes (T2D) prevalence is a global public health concern. The aetiology of T2D has not been fully elucidated and this is hampering the development of effective preventative and curative interventions to curb the T2D burden. Although much has been done to elucidate the environmental risk factors associated with T2D, little is known about the precise genetic risk factors that predispose people to it. There is limited knowledge about the common variants associated with T2D risk in the black South African population. However, evidence of shared common variants associated with T2D among people of different ethnicities has been documented. Nonetheless, the majority of the common variants that have been reported to be associated with T2D in other ethnicities are still yet to be evaluated in the black South African population. Objectives: The aim of this study was to evaluate the association of previously reported common genetic variants with T2D susceptibility, as indicated by impaired glucose tolerance (IGT), in a black South African population of Tswana descent. Methods: This study was a case-control study of 180 cases and 180 controls nested in the Prospective Urban Rural Epidemiology (PURE) study baseline data, which was collected in 2005. The DNA samples of the participants were genotyped for 77 single nucleotide polymorphisms (SNPs), using Illumina® VeraCode technology on the BeadXpress® platform. The gPlink software was used to evaluate the standard genetic models of disease penetrance for the association of the common variants with impaired glucose tolerance (IGT) while adjusting for age, sex and body mass index. Results: Four out of the 66 SNPs that were evaluated through the genetic association tests in this study were noted to be significantly associated with IGT (p< 0.05). Of the four SNPs, only rs1436955 was associated with an increase in T2D risk, while the other three variants, rs831571, rs8050136 and rs7542900, were noted to be associated with a decreased risk of T2D. However, none of the four SNPs was significantly associated with IGT after correcting for multiple testing (p <0.05). Conclusions: Black South Africans of Tswana descent might not share common variants associated with T2D risk, as indicated by IGT in other ethnicities. Wellpowered studies are required to evaluate the association of common variants with T2D risk in this population group. The results from this study emphasise the need for population-specific variants to assess the genetic susceptibility of complex diseases such as T2D in the black South African population. / MSc (Nutrition), North-West University, Potchefstroom Campus, 2014

Introduction: The continual increase of type 2 diabetes (T2D) prevalence is a global public health concern. The aetiology of T2D has not been fully elucidated and this is hampering the development of effective preventative and curative interventions to curb the T2D burden. Although much has been done to elucidate the environmental risk factors associated with T2D, little is known about the precise genetic risk factors that predispose people to it. There is limited knowledge about the common variants associated with T2D risk in the black South African population. However, evidence of shared common variants associated with T2D among people of different ethnicities has been documented. Nonetheless, the majority of the common variants that have been reported to be associated with T2D in other ethnicities are still yet to be evaluated in the black South African population. Objectives: The aim of this study was to evaluate the association of previously reported common genetic variants with T2D susceptibility, as indicated by impaired glucose tolerance (IGT), in a black South African population of Tswana descent. Methods: This study was a case-control study of 180 cases and 180 controls nested in the Prospective Urban Rural Epidemiology (PURE) study baseline data, which was collected in 2005. The DNA samples of the participants were genotyped for 77 single nucleotide polymorphisms (SNPs), using Illumina® VeraCode technology on the BeadXpress® platform. The gPlink software was used to evaluate the standard genetic models of disease penetrance for the association of the common variants with impaired glucose tolerance (IGT) while adjusting for age, sex and body mass index. Results: Four out of the 66 SNPs that were evaluated through the genetic association tests in this study were noted to be significantly associated with IGT (p< 0.05). Of the four SNPs, only rs1436955 was associated with an increase in T2D risk, while the other three variants, rs831571, rs8050136 and rs7542900, were noted to be associated with a decreased risk of T2D. However, none of the four SNPs was significantly associated with IGT after correcting for multiple testing (p <0.05). Conclusions: Black South Africans of Tswana descent might not share common variants associated with T2D risk, as indicated by IGT in other ethnicities. Wellpowered studies are required to evaluate the association of common variants with T2D risk in this population group. The results from this study emphasise the need for population-specific variants to assess the genetic susceptibility of complex diseases such as T2D in the black South African population. / MSc (Nutrition), North-West University, Potchefstroom Campus, 2014

Introduction: In Africa, it is estimated that cardiovascular disease (CVD) will affect approximately 1.3 million people per annum over the following 20 years. C-reactive protein (CRP) is a predictor of CVD risk and certain CRP gene polymorphisms can result in altered CRP concentrations. The distribution of CRP gene polymorphisms is ethnic-specific and extrapolating information from other populations to the black South African population, reported to harbour considerable genetic variation, should be avoided. This highlights the fact that genetic research among black South Africans is necessary. Objectives: The main aim of this dissertation was to determine the association between various polymorphisms (reported and novel [single nucleotide polymorphisms (SNPs)] within the CRP gene with CRP concentrations [measured as high sensitivity (hs)-CRP concentrations] in a black South African population undergoing an epidemiological transition. Interactions between specific CRP polymorphisms and certain environmental factors on hs-CRP concentrations were also investigated. Methods: This cross-sectional study (n=1,588) was nested within the Prospective Urban and Rural Epidemiological (PURE) study. Genotyping was performed using Illumina VeraCode technology on the BeadXpress® platform. Hs-CRP concentrations were measured by the use of a sequential multiple analyser computer (SMAC) through a particle-enhanced immunoturbidometric assay. Results: All the SNPs adhered to the assumptions of Hardy-Weinberg equilibrium, although the distribution of several SNPs differed from that reported in other population groups. Three SNPs (rs3093058, rs3093062 and rs3093068) were associated with a significant (p ≤ 0.05) increase in CRP concentrations. Five SNPs (rs1205, rs1341665, rs2794520, rs7553007 and rs2027471) were associated with a significant (p ≤ 0.05) decrease in CRP concentrations. This difference in effect was most probably due to changes in gene function brought about by the localisation of these SNPs in the CRP gene. Men and urban individuals were more likely to present with significant associations between the SNPs investigated and CRP concentrations. The difference in the prevalence of the alleles associated with higher CRP concentrations in this population compared to non-African populations could possibly explain the increased CRP concentrations that are observed in the black South African population. Gene-gender (rs1205, rs1341665 and rs2027474) as well as gene-environmental (rs3093068) interactions were also observed. Conclusions: CRP concentrations are in themselves a complex trait and there are many factors at play that influence their expression. Numerous factors (both genetic and environmental) are involved and no single factor acting alone is likely to have enough of an influence to be used as a clinical diagnostic test of CRP concentrations. These results provide valuable information on the regulation of CRP in a black South African population as well as contribute to the literature of CRP on a global level. / Thesis (MSc (Nutrition))--North-West University, Potchefstroom Campus, 2013.

Introduction: In Africa, it is estimated that cardiovascular disease (CVD) will affect approximately 1.3 million people per annum over the following 20 years. C-reactive protein (CRP) is a predictor of CVD risk and certain CRP gene polymorphisms can result in altered CRP concentrations. The distribution of CRP gene polymorphisms is ethnic-specific and extrapolating information from other populations to the black South African population, reported to harbour considerable genetic variation, should be avoided. This highlights the fact that genetic research among black South Africans is necessary. Objectives: The main aim of this dissertation was to determine the association between various polymorphisms (reported and novel [single nucleotide polymorphisms (SNPs)] within the CRP gene with CRP concentrations [measured as high sensitivity (hs)-CRP concentrations] in a black South African population undergoing an epidemiological transition. Interactions between specific CRP polymorphisms and certain environmental factors on hs-CRP concentrations were also investigated. Methods: This cross-sectional study (n=1,588) was nested within the Prospective Urban and Rural Epidemiological (PURE) study. Genotyping was performed using Illumina VeraCode technology on the BeadXpress® platform. Hs-CRP concentrations were measured by the use of a sequential multiple analyser computer (SMAC) through a particle-enhanced immunoturbidometric assay. Results: All the SNPs adhered to the assumptions of Hardy-Weinberg equilibrium, although the distribution of several SNPs differed from that reported in other population groups. Three SNPs (rs3093058, rs3093062 and rs3093068) were associated with a significant (p ≤ 0.05) increase in CRP concentrations. Five SNPs (rs1205, rs1341665, rs2794520, rs7553007 and rs2027471) were associated with a significant (p ≤ 0.05) decrease in CRP concentrations. This difference in effect was most probably due to changes in gene function brought about by the localisation of these SNPs in the CRP gene. Men and urban individuals were more likely to present with significant associations between the SNPs investigated and CRP concentrations. The difference in the prevalence of the alleles associated with higher CRP concentrations in this population compared to non-African populations could possibly explain the increased CRP concentrations that are observed in the black South African population. Gene-gender (rs1205, rs1341665 and rs2027474) as well as gene-environmental (rs3093068) interactions were also observed. Conclusions: CRP concentrations are in themselves a complex trait and there are many factors at play that influence their expression. Numerous factors (both genetic and environmental) are involved and no single factor acting alone is likely to have enough of an influence to be used as a clinical diagnostic test of CRP concentrations. These results provide valuable information on the regulation of CRP in a black South African population as well as contribute to the literature of CRP on a global level. / Thesis (MSc (Nutrition))--North-West University, Potchefstroom Campus, 2013.