Genetics and Epigenetic in Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) (OMIM #152700) is the prototype of a multiorgan autoimmune disease and still considered as a disease with an ambiguous etiology. The disease predominantly affects women during the reproductive years at a ratio of eight women per one man (Lopez, 2003). Its pathogenesis is multifactorial lying on genetic and environmental factors in which it occurs in genetically-predisposed individuals who have experienced certain environmental triggers resulting in an irreversible loss of immunologic self-tolerance. The nature of these environmental triggers is largely unknown. It is most likely that it requires a number of environmental triggers occurring together or sequentially over a limited period of time. The concept has therefore emerged of ‘threshold liability’ in which disease develops when a threshold of genetic and environmental susceptibility effects is reached (Jonsen,2007). Epigenetics, the control of gene packaging and expression independent of alterations in the DNA sequence, is providing new directions linking genetics and environmental factors. It has become clear that besides genetics, epigenetics plays a major role in complex diseases with complex immunological pathogenesis like lupus. Convincing evidence indicates that epigenetic mechanisms, and in particular impaired T cell DNA methylation, provide an additional factor. Interpreting the precise contribution of epigenetic factors to autoimmunity, and in particular to SLE, has become an active research area. Herein, we will discuss our current understanding of SLE as an autoimmune disease and as a complex genetic disorder. Through the review of the current list of best validated SLE disease susceptibility candidate genes, in particular considering how the known and potential function of these genes may allow us to articulate the genetic of SLE pathogenesis. In addition we will review the effect of epigenetics on SLE pathology.