The Genetics of Atopic Eczema in the Bangladeshi population of East London

Abstract

Atopic Eczema (AE) is a common, complex, genetic skin disease. It usually begins in infancy and can affect any part of the body but often occurs in the flexures of the elbows and knees. The cohort used in this study is of Bangladeshi origin and all subjects reside in East London. Using a combination of techniques, such as the Illumina goldengate assay, PCR and sequencing, both novel and previously associated genes have been studied in this thesis. Previously associated genes were used to validate this population and also to investigate the variation of genes associated in different ethnic populations. Six of eleven previously associated genes were replicated in this population. In order to identify novel genes of interest in AE, sixteen novel genes were chosen for investigation. Of these sixteen, eight showed association with AE. A recently identified gene involved in the pathogenesis of AE, Filaggrin (FLG), was also investigated. This was done using a combination of PCR, sequencing and Taqman SNP assays. Only six families out of 80 in this population were found to harbour the two known common FLG mutations. These families were clinically reassessed for Ichthyosis Vulgaris (IV) which is also associated to the same FLG mutations. After this reassessment the FLG mutations were shown to be associated with IV in this population with variable penetrance. No association with AE was found. ABCA12 was also investigated as a candidate gene for AE, again using the Illumina goldengate assay and microsatellite linkage markers. Association was observed with this gene and AE. Harlequin Ichthyosis (HI) mutations were also screened in this gene for twelve additional HI patients. This thesis has provided a greater insight into the variation of gene associations between populations with AE, highlighting novel genes, including KY-NU and JAK3/INSL3, which need to be investigated in other populations.