South Africa is at present encountering one of the worst Tuberculosis (TB) epidemics in the world, accentuating the need for intervention to eradicate TB. Various studies have established that certain population groups are at risk for increased susceptibility to infection with Mycobacterium tuberculosis (M. tuberculosis). This predominantly occurs in populations, like the native African population groups, who were not exposed to TB until the disease arrived in their country with European settlers, colonialists and missionaries. These population groups consequently lack the natural resistance to infection, which other populations developed through years of exposure to the pathogen. Several susceptibility-associated genetic polymorphisms have been proposed to explain differential susceptibility to TB. HLA class II molecules play a pivotal role in the activation of the host immune response against M. tuberculosis. Consequently numerous HLA class II genes have been found to be associated with TB. Among the most commonly observed associations is that of HLA-DR2 with TB, which has been observed in various population groups. Although this association has been observed to transcend ethnic barriers, inter-population variation has also been established regarding HLA-TB associations. In this study, the possible association of HLA class II polymorphisms, specifically of the HLA-DRB1, DQB1, DRB3, DRB4 and DRB5 loci, with TB susceptibility was investigated in the Venda population of South Africa. This was achieved by conducting both a case-control and family-based association study. The results obtained in this study established a unique association between HLA-DRB1*1302, DQ7 and TB susceptibility. A marginally significant association was also observed with DRB1*1301 and DQ6d and possible TB resistance. The above-mentioned results, which were observed in the case-control group, could not be replicated in the family-based study. It was therefore concluded from the results obtained in this study that employing both a case-control and family-based analysis when undertaking an association study is the most beneficial option. / Prof. Liza Bornman
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uj/uj:7258 |
| Date | 15 May 2008 |
| Creators | Lombard, Zane |
| Source Sets | South African National ETD Portal |
| Detected Language | English |
| Type | Thesis |
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