Genetic epidemiology of juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of disorders. Although the pathogenesis is not completely understood, many studies point to a genetic component in the susceptibility for this disease with environmental factors also contributing to the pathogenesis. The genetic component of JIA is complex, involving the effects of multiple genes at various points in the disease pathology. The best documented association is with the genes within the Human Leukocyte Antigen (HLA) complex, encoding the classical peptide-presenting molecules. JIA is associated with particular alleles at, at least, three different HLA loci: HLA-A (HLA-A*0201), -DR/DQ (DRB1*08, DRB1*11, DRB1*13) and -DP (DPB1*0201, DPB1*0301), with marked differences between the disease subtypes. Non-HLA genes may also contribute to the disease. Many of these genes encode cytokines and probably regulate their production. Examples of such cytokines involved in JIA are interleukin-1 alpha (IL-1 alpha), interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), interleukin-10 (IL-10), macrophage inhibitory factor (MIF), interferon regulatory transcription factor (IFN1). Accumulated data suggest that interactions between the genes are necessary for the development of the disease. Knowledge of the genes involved would help to understand the molecular mechanisms involved in the pathogenesis of JIA and may have implications for prognosis and therapy.