Genetic analysis of candidate genes linked to atopic eczema in the Bangladeshi population of East London

Abstract

Background: Atopic Eczema (AE) is a common skin disease that results from a complex interplay between genetic and environmental factors. It may be associated with other atopic phenotypes including; asthma, hayfever and food allergy. The onset, typically in early childhood, can affect any part of the body but often occurs in the flexures of the elbows and knees. Aim and hypothesis: The aim of this thesis was to investigate the genetics of AE in the Bangladeshi families of East London to identify possible positive association with AE or other atopic diseases. This involved investigating previously associated genes and also novel genes mapping to regions showing suggestive linkage from a microsatellite genome scan and data from a haplotype tagging SNP based Illumina based Array genotyping. Methods: A total of 70 families (n=384) individuals were recruited via the Paediatric dermatology Clinic at the Royal London Hospital. Three genes; FOXP3, SPINK5 and TNC were assessed for genetic association with AE and other atopic phenotypes using a combination of techniques, such as PCR, dHPLC, sequencing, and Taqman SNP assays. FBAT software was used for statistical analysis. Results and future work: Suggestive associations with AE and other allergic disorders were identified in all genes examined however, none of these results remained significant (p-value<0.05) after correcting for multiple testing. As part of this project, several novel genes have been identified including TNC, JAK3 and KYNU. To follow up these promising findings, replication studies could be conducted in other populations with AE in particular by large case-control analyses. In addition, with the development of high throughput SNP genotyping and, in particular, exome sequencing, the larger Bangladeshi families with multiple AE affected could be investigated to identify AE-associated disease mutations