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Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans
Background: Asthma and allergic disease are the result of a complex interaction between genetic predisposition and environmental exposure. It is likely that multiple genes are involved in the progression from allergen exposure to the development of signs and symptoms of allergic disease. Although ad...
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| Format: | Thesis |
| Language: | English |
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Department of Paediatrics and Child Health
2017
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| _version_ | 1867613163724210176 |
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| access_status_str | Open Access |
| author | Laurence, Craig |
| author2 | Levin, Michael |
| author_browse | Laurence, Craig Levin, Michael |
| author_facet | Levin, Michael Laurence, Craig |
| author_sort | Laurence, Craig |
| collection | Thesis |
| description | Background: Asthma and allergic disease are the result of a complex interaction between genetic predisposition and environmental exposure. It is likely that multiple genes are involved in the progression from allergen exposure to the development of signs and symptoms of allergic disease. Although advances in genetic research have progressed exponentially in the past twenty years, and a growing body of evidence from the developed world has yielded several promising candidate polymorphisms, the precise nature of the genetic basis for allergic disease remains to be elucidated. In addition, there is a paucity of literature in this field from the developing world, and for people of African origin in particular. Several studies suggest that the prevalence of asthma and allergic disease in South Africa has increased significantly over the past forty years, at a rate that is too rapid to be explained by genetic modification. A likely explanation for this trend is that an increasing number of genetically susceptible individuals are being exposed to environmental stimuli that are critical to the formation of allergic disease. It is possible, although unproven, that evolutionary adaptation of inflammatory immune responses may increase the genetic predisposition to allergic disease amongst people of Black African origin. This thesis represents the first analysis of several single nucleotide polymorphisms (SNPs) with regards to their prevalence in the Xhosa population, as well as the correlation between these SNPs and clinical and laboratory markers of allergic disease in this population. Methods: A cross-sectional sample of about 300 unrelated Xhosa school children was obtained from a local high school. Phenotypic data was collected in the form of a symptom questionnaire, blood samples for total IgE as well as IgE to Ascaris lumbricoides, skin prick tests to common local food and aeroallergens, as well as a modified methacholine challenge to establish the prevalence of bronchial hyper-reactivity. In addition, genotyping was performed to investigate the prevalence of twenty-seven SNPs in this population. We aimed to establish a baseline of the prevalence of potential pro-inflammatory alleles (PIAs), as well as to investigate the relationship between these PIAs and clinical and laboratory markers of asthma and allergic disease. Results: We found several significant associations between several SNPs and allergic disease, specifically in genes relating to the development of immune tolerance (IL-10), genes relating to TH1 inflammation (IL-12 and IFNGR1) and genes relating to TH2 inflammation (IL-4, IL- 4R, IL-13). Unfortunately, the generalizability of our findings is limited by, amongst others, the selection of pupils from a single school and the use of self-reported end points as markers of clinical phenotypes rather than physician diagnosed allergic illnesses. Conclusion: This is the first trial of its kind in the Xhosa population. Despite the limitations described above, we feel that this study has provided valuable baseline prevalence data, and unearthed some interesting associations between PIAs and allergic disease. We would welcome further research in this population to confirm or refute our findings. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/22821 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:31:47.142Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| publisher | Department of Paediatrics and Child Health |
| publisherStr | Department of Paediatrics and Child Health |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/22821 Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans Laurence, Craig Levin, Michael Paediatrics Background: Asthma and allergic disease are the result of a complex interaction between genetic predisposition and environmental exposure. It is likely that multiple genes are involved in the progression from allergen exposure to the development of signs and symptoms of allergic disease. Although advances in genetic research have progressed exponentially in the past twenty years, and a growing body of evidence from the developed world has yielded several promising candidate polymorphisms, the precise nature of the genetic basis for allergic disease remains to be elucidated. In addition, there is a paucity of literature in this field from the developing world, and for people of African origin in particular. Several studies suggest that the prevalence of asthma and allergic disease in South Africa has increased significantly over the past forty years, at a rate that is too rapid to be explained by genetic modification. A likely explanation for this trend is that an increasing number of genetically susceptible individuals are being exposed to environmental stimuli that are critical to the formation of allergic disease. It is possible, although unproven, that evolutionary adaptation of inflammatory immune responses may increase the genetic predisposition to allergic disease amongst people of Black African origin. This thesis represents the first analysis of several single nucleotide polymorphisms (SNPs) with regards to their prevalence in the Xhosa population, as well as the correlation between these SNPs and clinical and laboratory markers of allergic disease in this population. Methods: A cross-sectional sample of about 300 unrelated Xhosa school children was obtained from a local high school. Phenotypic data was collected in the form of a symptom questionnaire, blood samples for total IgE as well as IgE to Ascaris lumbricoides, skin prick tests to common local food and aeroallergens, as well as a modified methacholine challenge to establish the prevalence of bronchial hyper-reactivity. In addition, genotyping was performed to investigate the prevalence of twenty-seven SNPs in this population. We aimed to establish a baseline of the prevalence of potential pro-inflammatory alleles (PIAs), as well as to investigate the relationship between these PIAs and clinical and laboratory markers of asthma and allergic disease. Results: We found several significant associations between several SNPs and allergic disease, specifically in genes relating to the development of immune tolerance (IL-10), genes relating to TH1 inflammation (IL-12 and IFNGR1) and genes relating to TH2 inflammation (IL-4, IL- 4R, IL-13). Unfortunately, the generalizability of our findings is limited by, amongst others, the selection of pupils from a single school and the use of self-reported end points as markers of clinical phenotypes rather than physician diagnosed allergic illnesses. Conclusion: This is the first trial of its kind in the Xhosa population. Despite the limitations described above, we feel that this study has provided valuable baseline prevalence data, and unearthed some interesting associations between PIAs and allergic disease. We would welcome further research in this population to confirm or refute our findings. 2017-01-19T12:24:15Z 2017-01-19T12:24:15Z 2016 Master Thesis Masters MMed http://hdl.handle.net/11427/22821 eng application/pdf Department of Paediatrics and Child Health Faculty of Health Sciences University of Cape Town |
| spellingShingle | Paediatrics Laurence, Craig Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans |
| thesis_degree_str | Master's |
| title | Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans |
| title_full | Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans |
| title_fullStr | Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans |
| title_full_unstemmed | Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans |
| title_short | Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans |
| title_sort | correlation between pro inflammatory alleles and clinical and laboratory markers of allergy in xhosa south africans |
| topic | Paediatrics |
| url | http://hdl.handle.net/11427/22821 |
| work_keys_str_mv | AT laurencecraig correlationbetweenproinflammatoryallelesandclinicalandlaboratorymarkersofallergyinxhosasouthafricans |