HLA complex genes in type 1 diabetes and other autoimmune diseases. Which genes are involved?

The predisposition to develop a majority of autoimmune diseases is associat ed with specific genes within the human leukocyte antigen (HLA) complex. Ho wever, it is frequently difficult to determine which of the many genes of t he HLA complex are directly involved in the disease process. The main reaso ns for these difficulties are the complexity of associations where several HLA complex genes might be involved, and the strong linkage disequilibrium that exists between the genes in this complex. The latter phenomenon leads to secondary disease associations, or what has been called 'hitchhiking pol ymorphisms'. Here, we give an overview of the complexity of HLA association s in autoimmune disease, focusing on type 1 diabetes and trying to answer t he question: how many and which HLA genes are directly involved?