Genes mediating environment interactions in type 1 diabetes.

The relative risk of type 1 (autoimmune) diabetes mellitus for a sibling of an affected patient is fifteen times that of the general population, indicating a strong genetic contribution to the disease. Yet, the incidence of diabetes in most Western communities has doubled every fifteen years since the Second World War - a rate of increase that can only possibly be explained by a major etiological effect of environment. Here, the authors provide a selective review of risk factors identified to date. Recent reports of linkage of type 1 diabetes to genes encoding pathogen pattern recognition molecules, such as toll-like receptors, are discussed, providing a testable hypothesis regarding a mechanism by which genetic and environmental influences on disease progress are integrated.