Background Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by a broad spectrum of clinical and serological manifestations. This may reflect a complex and multifactorial etiology involving several identified genetic and environmental factors, though not explaining the full risk of SLE. Established SLE risk genotypes are either very rare or with modest effect sizes and twin studies indicate that other factors besides genetics must be operative in SLE etiology. The exposome comprises the cumulative environmental influences on an individual and associated biological responses through the lifespan. It has been demonstrated that exposure to silica, smoking and exogenous hormones candidate as environmental risk factors in SLE, while alcohol consumption seems to be protective.

Methods A systematic search on published studies that have investigated interactions between genetic and environmental risk factors resulted in five studies based on three different populations. Available measures of interaction were extracted.

Results Very few (n=5) studies have investigated potential gene-environment interactions to determine if some of the unexplained SLE risk is attributable hereto. Even less (n=2) have focused on interactions between specific risk genotypes and environmental exposures relevant to SLE pathogenesis. Cohort and case-control studies may provide data to suggest such biological interactions and various statistical measures of interaction can indicate the magnitude of such. However, such studies do often have very large sample-size requirements and it is suggested that the rarity of SLE to some extent can be compensated by increasing the ratio of controls.

Conclusions This review summarizes the current body of knowledge on gene-environment interactions in SLE. We argue for the prioritization of studies that comprise the increasing details available of the genome and exposome relevant to SLE as they have the potential to disclose new aspects of SLE pathogenesis including phenotype heterogeneity.

Funding Source(s): Gigtforeningen