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 glutation 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.

High α‐defensin levels in patients with systemic lupus erythematosus

“…1,2 The precise aetiology of SLE is unknown, but hormonal, 3 genetic, 4 viral, 5 and environmental factors 6 appear to play a role in the development and course of the disease. SLE is characterized by the production of a variety of autoantibodies and impaired function of B and T cells.…”

Proteomic analysis of human plasma and peripheral blood mononuclear cells in Systemic Lupus Erythematosus patients

“…It is well established that certain drugs induce autoantibodies in a significant number of patients. Newer biologics and antiviral agents have been reported to cause drug-induced lupus (DIL) [23]. Socioeconomic factors have been associated with poorer outcomes and higher disease activity, [24] although it remains unclear whether they play a role in disease susceptibility or subsequent progression.…”

Association between functionalIRF7variant and systemic lupus erythematosus may need more critical examination: Comment on the article by Fu et al

“…Although genetic factors contribute substantially to SLE susceptibility, many environmental factors have been shown to be associated with the development of SLE (2). An analysis adjusted for potential environmental risk factors (for example, ultraviolet light, medications, smoking, and alcohol consumption) should be performed, and may provide more precise information on the genetic contribution of IRF7 to SLE etiology.…”

“…The development of SLE is a multistage, multifactorial, and long-term process (2,3), and a single polymorphism might have limited impact on SLE susceptibility. More comprehensive multiple polymorphism-based or haplotypebased strategies, rather than a single polymorphism-based strategy, may provide more precise information.…”