Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans

dc.contributor.advisorLevin, Michaelen_ZA
dc.contributor.authorLaurence, Craigen_ZA
dc.date.accessioned2017-01-19T12:24:15Z
dc.date.available2017-01-19T12:24:15Z
dc.date.issued2016en_ZA
dc.description.abstractBackground: 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.en_ZA
dc.identifier.apacitationLaurence, C. (2016). <i>Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Department of Paediatrics and Child Health. Retrieved from http://hdl.handle.net/11427/22821en_ZA
dc.identifier.chicagocitationLaurence, Craig. <i>"Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Department of Paediatrics and Child Health, 2016. http://hdl.handle.net/11427/22821en_ZA
dc.identifier.citationLaurence, C. 2016. Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Laurence, Craig AB - 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. DA - 2016 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2016 T1 - Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans TI - Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans UR - http://hdl.handle.net/11427/22821 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/22821
dc.identifier.vancouvercitationLaurence C. Correlation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africans. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Department of Paediatrics and Child Health, 2016 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/22821en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDepartment of Paediatrics and Child Healthen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherPaediatricsen_ZA
dc.titleCorrelation between pro-inflammatory alleles and clinical and laboratory markers of allergy in Xhosa South Africansen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMMeden_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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