Screening black South African females with Type 2 Diabetes Mellitus for mutations in the peroxisome proliferator-activated receptor gamma gene
| dc.contributor.advisor | Marx, G. M. | |
| dc.contributor.advisor | Goedhals, D. | |
| dc.contributor.author | Nienaber, Elzette | |
| dc.date.accessioned | 2016-11-15T14:16:23Z | |
| dc.date.available | 2016-11-15T14:16:23Z | |
| dc.date.issued | 2016-01 | |
| dc.description.abstract | English: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder which is caused by a combination of an inadequate response to insulin secretion and a resistance to insulin action. The peroxisome proliferator-activated receptor gamma (PPARG) gene has been established as one of the major genes to have an impact on the risk of T2DM. The Pro12Ala polymorphism is one of the most common mutations found within PPARG and has been described in many different populations. However, it has not yet been established whether the Pro12Ala variant has a significant association with T2DM in the black, female South African population. The aim of this study was to screen for novel T2DM genetic risk factors in the PPARG gene and to determine the presence of previously identified T2DM genetic risk factors in black South-African women with T2DM. Quantitative PCR was performed on 184 black female South African participants that consisted of 93 patients diagnosed with T2DM and 91 control participants. Quantitative PCR was used to screen for the presence of the Pro12Ala polymorphism in the PPARG gene. Next Generation Sequencing (NGS) was performed on eight patients and eight control samples which were individually matched according to age and body mass index (BMI). NGS was used to identify novel polymorphisms which might be associated with T2DM and to detect the prevalence of previously described variants within the PPARG gene. The qPCR genotyping results showed that of the 184 participants, 183 had the Pro/Pro genotype and only one had the heterozygous Pro/Ala genotype. The Ala/Ala genotype was not detected in this study population. Although the study sample is only a small representation of the total population, it can be derived from the results that it is likely that the Ala/Ala genotype is rare in the population. Additionally, NGS results identified two variants within three individuals of the selected sample. The one variant (rs41516544) did not show any clinical relevance and is probably just a rare population variant. The other variant (rs3856806) is a well-described polymorphism and has been associated with having a protective effect against T2DM and was present in a control participant. This variant might be significant in its association to T2DM in the black South African population but will have to be further investigated in future studies. | en_ZA |
| dc.description.abstract | Afrikaans: Tipe 2 diabetes mellitus (T2DM) is 'n kroniese metaboliese afwyking wat veroorsaak word deur 'n kombinasie van 'n onvoldoende reaksie op insulien afskeiding en 'n weerstand teen insulien aksie. Die peroxisoom proliferator-geaktiveerde reseptor-gamma 2 (PPARG-2) geen word beskou as een van die belangrikste gene wat 'n impak op die risiko van T2DM het. Die Pro12Ala polimorfisme is een van die mees algemene mutasies wat in die PPARG geen aangetref word en is al beskryf in verskillende bevolkingsgroepe. Dit is nog nie vasgestel of die Pro12Ala variant 'n beduidende assosiasie met T2DM in die swart, vroulike populasie van Suid-Afrika het nie. Die doel van hierdie studie was om te toets vir nuwe T2DM genetiese risikofaktore in die PPARG geen en om die teenwoordigheid van voorheen geïdentifiseerde T2DM genetiese risikofaktore in swart Suid-Afrikaanse vroue met T2DM te bepaal. Reële-tyd polimerase ketting reaksie (Reële-tyd PKR) is uitgevoer op 184 swart vroulike Suid-Afrikaanse deelnemers wat bestaan uit 93 individue wat met T2DM gediagnoseer is en 91 individue wat dien as kontroles. Reële-tyd PKR is gebruik om te toets vir die teenwoordigheid van die Pro12Ala polimorfisme in die PPARG gene. Volgende Generasie Volgordebepaling (VGV) is uitgevoer op agt pasiënte en agt kontrole individue wat ooreengestem het in terme van ouderdom en liggaamsmassa-indeks (BMI). VGV is gebruik om nuwe polimorfismes te identifiseer wat moontlik geassosieer kan word met T2DM en om die voorkoms van variante wat voorheen beskryf is in PPARG te bepaal. Die Reële-tyd PKR genotipering resultate het getoon dat van die 184 deelnemers 183 die Pro/Pro genotype vertoon en net een die heterosigotiese Pro/Ala genotype het. Die Ala/Ala genotipe is nie teenwoordig in hierdie studiepopulasie nie. Alhoewel die studiepopulasie slegs 'n klein verteenwoordiging van die totale bevolking is dui die resultate daarop dat die Ala/Ala genotipe waarskynlik baie skaars in die bevolking is. VGV resultate het 2 variante geïdentifiseer in drie individue van die studiegroep. Die een variant (rs41516544) het geen kliniese relevansie nie en is waarskynlik net 'n seldsame bevolkings variant. Die ander variant (rs3856806) is 'n goed beskryfde polimorfisme wat geassosieer is met 'n beskermende effek teen T2DM. Hierdie variant kan moontlik betekenisvol wees in die swart Suid-Afrikaanse bevolking, maar sal eers verder ondersoek moet word deur toekomstige studies. | en_ZA |
| dc.description.sponsorship | National Research Foundation (NRF) Thuthuka grant | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11660/4545 | |
| dc.language.iso | en | en_ZA |
| dc.publisher | University of the Free State | en_ZA |
| dc.rights.holder | University of the Free State | en_ZA |
| dc.subject | AmpliSeq™ | en_ZA |
| dc.subject | Ion Torrent PGM™ | en_ZA |
| dc.subject | Next generation sequencing | en_ZA |
| dc.subject | NGS data-analysis | en_ZA |
| dc.subject | Peroxisome proliferator-activated receptor gamma (PPARG) | en_ZA |
| dc.subject | Pro12Ala | en_ZA |
| dc.subject | qPCR | en_ZA |
| dc.subject | Type 2 diabetes mellitus | en_ZA |
| dc.subject | Women, Black -- South Africa | en_ZA |
| dc.subject | Dissertation (M.Med.Sc. (Haematology and Cell Biology))--University of the Free State, 2016 | en_ZA |
| dc.title | Screening black South African females with Type 2 Diabetes Mellitus for mutations in the peroxisome proliferator-activated receptor gamma gene | en_ZA |
| dc.type | Dissertation | en_ZA |