CpG islands of the vitamin D receptor gene : differential methylation and tuberculosis predisposition

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dc.contributor.advisor Prof. Liza Bornman; Dr. Gerrit Koorsen en
dc.contributor.author Andraos, Charlene
dc.date.accessioned 2011-06-29T06:40:34Z
dc.date.available 2011-06-29T06:40:34Z
dc.date.issued 2011-06-29T06:40:34Z
dc.date.submitted 2010-01
dc.identifier.uri http://hdl.handle.net/10210/3731
dc.description M.Sc. en
dc.description.abstract Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M. tuberculosis). TB is a multifactorial disease, influenced by both environmental and genetic factors. Susceptibility varies among individuals and is likely explained by differential environmental exposures and genetic factors. For example, Africans are more susceptible to TB than non-Africans, likely attributed to their generally lower socioeconomic status and possible higher frequencies of ‘susceptible’ genetic variants. Similarly, males are more susceptible to TB than females, presumably as a consequence of gender-based sociocultural differences as well as biological and/or genetic differences. From a host genetic perspective, TB is a complex disease associated with variants from several genes. The Vitamin D Receptor (VDR) gene, coding for the VDR protein, has received much attention as a candidate gene; the VDR mediates vitamin D functions, of which one is to restrict M. tuberculosis survival in macrophages. Several studies attempting to associate VDR single nucleotide polymorphisms (SNPs) with TB susceptibility have given inconsistent results. Factors suggested to contribute to these inconsistencies include confounding environmental factors as well as higher VDR genetic/haplotypic diversity and less linkage disequilibrium (LD) in African populations compared to non-African populations. However, epigenetic variation has not yet been considered as an additional confounding factor leading to inconsistencies in genetic association studies for TB and VDR. vi Epigenetic factors are heritable and pivotal to regulate gene transcription. Moreover, epigenetic factors are highly susceptible to environmental influences and have been shown to be the underlying factor in certain disease aetiologies. Not only are epigenetic factors susceptible to environmental influences, but also to genetic factors acting in cis or in trans. An example is the formation or elimination of a methylatable CpG by a SNP. On the other hand, epigenetic factors may influence the genotype through formation of methylation-induced SNPs. The synergistic effect of genetic variants, epigenetic variants and the environment on disease is known as the common disease genetic epigenetic (CDGE) hypothesis. The CDGE hypothesis supports the study of both genetic and epigenetic variants to provide a better understanding of disease aetiologies and to increase the power of association studies. en
dc.language.iso en en
dc.subject Tuberculosis
dc.subject Disease susceptibility
dc.subject Cell receptors
dc.subject Vitamin D
dc.subject Human genetics
dc.title CpG islands of the vitamin D receptor gene : differential methylation and tuberculosis predisposition en
dc.type Thesis en

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