Gene–environment interactions in the aetiology of systemic lupus erythematosus

Abstract

Systemic lupus erythematosus (SLE) is a disease that displays a multitude of symptoms and a vast array of autoantibodies. The disease course may vary substantially between patients. The current understanding of SLE aetiology includes environmental factors acting on a genetically prone individual during an undetermined time period resulting in autoimmunity and finally surpassing that individual's disease threshold. Genetic differences and environmental factors may interact specifically in the pathogenetic processes and may influence disease development and modify the disease course. Identification of these factors and their interactions in the pathogenesis of SLE is vital in understanding the disease and may contribute to identify new treatment targets and perhaps also aid in disease prevention. However, there are several problems that need to be overcome, such as the protracted time frame of environmental influence, time dependent epigenetic alterations and the possibility that different pathogenetic pathways may result in a similar disease phenotype. This is mirrored by the relatively few studies that suggest specific gene-environment interactions. These include an association between SLE diagnosis and glutathion S-transferase gene variants combined with occupational sun exposure as well as variants of the N-acetyl transferase gene in combination with either aromatic amine exposure or hydralazine. With increased knowledge on SLE pathogenesis, the role of environmental factors and their genetic interactions may be further elucidated.

• SLE
• genetics
• epigenetics
• environment
• etiology

Acknowledgements

Supported by grants from the Swedish National Association Against Rheumatism, the Swedish Research Council (grants 13489 and 15092), the Medical Faculty of the University of Lund, Alfred Österlund's Foundation, The Crafoord Foundation, Greta and Johan Kock's Foundation, The King Gustaf V's 80th Birthday Fund, Lund University Hospital and Prof. Nanna Svartz' Foundation.