The goal of this application is to investigate the beta-defensin gene DEFB-1 and the beta-defensin gene cluster, DEFB4, DEFB103 and DEFB104, and the effect of genetic variations on susceptibility of fungal infection in immuno-compromised patients. The beta-defensin peptides have a variable expression pattern, and antifungal properties that are specific for each peptide. This proposal will extend the evidence that polymorphisms in genes encoding beta defensin peptides can be a useful diagnostic tool for screening susceptibility to oral Candida carriage and candidiasis. The utilization of genetic variations in the form of single nucleotide and copy number polymorphisms are becoming a recognizable tool for investigating the ? genetic basis of disease. The intention of the proposal is to develop and implement high-throughput methods for the clinical investigation of genetic variations in the four beta defensin genes, and correlate the findings with Candida carriage status, and medical findings at examination, on 300 patients that are at increased risk for Candida infection. Oral candidiasis is an opportunistic infection, prevalent in individuals with immune suppression due to infection, bone marrow and organ transplantation, and diabetes and other chemotherapeutic interventions. Oral Candida carriage is a risk factor for systemic infection in these individuals. The development and design of diagnostic assays to identify patients at risk could be beneficial as a clinical diagnostic, and will enhance the current information on defensin expression patterns and the association with development and progression of oral disease. ? ?
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